Ampi202018printswap1up 1..76

HEMATOLOGIC MALIGNANCIES—LYMPHOMA AND CHRONIC LYMPHOCYTIC LEUKEMIA

8000 Oral Abstract Session, Fri, 8:00 AM-11:00 AM

Is autologous transplantation (autoHCT) in relapsed diffuse large B-cell lymphoma (DLBCL) patients achieving only a PET/CT positive partial remission (PR) appropriate in the CAR-T cell era?

Nirav Niranjan Shah, Kwang Woo Ahn, Carlos Litovich, Timothy Fenske, Mehdi Hamadani; Medical College of Wisconsin, Milwaukee, WI; Division of Biostatistics, Institution for Health and Society, Medical College of Wisconsin, Milwaukee, WI; CIBMTR (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, WI; Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI

Background: In relapsed, chemosensitive DLBCL patients (pts), autoHCT consolidation is a standard therapy option. With the approval of anti-CD19 CAR T-cells in 2017, relapsed DLBCL pts with residual PET/CT avid disease after salvage therapies are increasingly being offered CAR T-cells in lieu of autoHCT. According to Center for International Blood and Marrow Transplant Research (CIBMTR) data in 2018, the number of autoHCT for DLBCL in the U.S. decreased by ~45% from prior years, likely due to application of CAR T-cells for both chemorefractory DLBCL and chemosensitive DLBCL pts not achieving a complete remission. Using the CIBMTR database, we report outcomes of autoHCT in relapsed chemosensitive DLBCL pts achieving only a PET/CT+ PR prior to HCT. Methods: 249 relapsed DLBCL pts undergoing an autoHCT from 2003-13 with a PET/CT+ PR prior to transplant were identified. The study cohort was divided into two groups: (a) early chemo-immunotherapy failure (ECF) defined as pts with primary refractory disease (PRefD) or relapse within 12 months of diagnosis, (b) late chemoimmunotherapy failure (LCF) defined as pts relapsing $12 months. Primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS) and relapse. Results: 182 pts had ECF and 67 pts had LCF. The median age of ECF pts was 57 years versus (vs) 63 years for LCF (p , 0.01). ECF pts more frequently had stage III-IV at diagnosis (74% vs 54%, p = , 0.01). 79% of ECF pts had PRefD. The most common conditioning regimen was BEAM in both cohorts. The adjusted 5-year probabilities for PFS and OS (ECF vs LCF) was not different between the 2 cohorts: 41% vs 41% (p = 0.93) and 51% vs 63% (p = 0.09), respectively. Cumulative incidence of relapse at 5 years in similar order was 48% vs 57%, p = 0.27. On multivariate analysis compared to the LCF, pts with ECF had an increased risk of death (HR = 1.61, 95%CI 1.05-2.46, p = 0.03) but no increased risk in PFS or relapse. Conclusions: Using the CIBMTR registry, we report outcomes of relapsed DLBCL pts in a PR with residual PET/CT avid disease at time of autoHCT. While OS favored LCF pts, the adjusted 5-year PFS (41%) was comparable in both cohorts. This 5 year PFS is comparable to results reported in historical trials of auto-HCT for DLBCL. With no randomized data demonstrating superiority of CAR T-cell therapy in chemosensitive PR patients, these findings strongly support that autoHCT should remain the current standard of care for this patient population. Research Sponsor: None.

8001 Oral Abstract Session, Fri, 8:00 AM-11:00 AM

Phase I Alexander study of AUTO3, the first CD19/22 dual targeting CAR T cell therapy, with pembrolizumab in patients with relapsed/refractory (r/r) DLBCL.

Wendy Osborne, Maria Marzolini, Eleni Tholouli, Aravind Ramakrishnan, Carlos R. Bachier, Peter A McSweeney, David Irvine, Michael Zhang, Muhammad Ali Al-Hajj, Martin Pule, Simon Thomas, Maud Jonnaert, Vijay Gopal Reddy Peddareddigari, Nushmia Z. Khokhar, Robert W. Chen, Kirit Ardeshna; Newcastle, Newcastle, United Kingdom; UCL, London, United Kingdom; Manchester Royal Infirmary, Manchester, United Kingdom; SCRI Austin St. Davids, Austin, TX; Texas Transplant Physician Group PLLC, San Antonio, TX; Colorado Blood Cancer Institute, Denver, CO; Glasgow Queen Elizabeth Uni- versity, Glasgow, United Kingdom; Autolus Therapeutics, London, United Kingdom; GlaxoSmithKline, Collegeville, PA; Janssen Pharmaceuticals, Collegeville, PA; City of Hope Medical Center, Duarte, CA; University College London Hospital, London, United Kingdom

Background: CD19 directed CAR T cells are effective in patients with r/r DLBCL, however relapses due to CD19 loss or PDL1 upregulation are common. In this study, we evaluate the safety and efficacy of AUTO3, a CAR T targeting CD19/22 with limited duration of PD-1 blockade. Methods: We constructed a bicistronic retroviral vector encoding both an anti-CD19 (OX40 co-stim) and an anti-CD22 (41BB co- stim) CAR with humanized binders. The cell product was manufactured in a semi-automated and closed process using CliniMACS Prodigy. Patients ($ 18 years) with r/r DLBCL (NOS) or transformed (tDLBCL); ECOG ,2, adequate organ function are eligible. Lymphodepletion was Flu/Cy prior to AUTO3. Bridging therapy was allowed. The three dose levels explored are 50, 150, and 450 x 10^6 CAR T cells. Patients received AUTO3 alone, or with 3 doses of pembrolizumab (pem) 200 mg q 3 wks starting on D14 (regimen A), or with a single dose of pem 200 mg on D-1 (regimen B). The primary endpoint is frequency of DLTs and grade (G) 3-5 adverse events (AE) and secondary endpoints included ORR, CRR, and biomarkers. Results: As of Jan 21, 2020, 28 patients underwent leukapheresis, 27 successfully manufactured, 1 being manufactured, and 19 patients treated with AUTO3. The median age was 57 (28 - 71) and median number of prior therapies was 3 (2 - 10). 89% had refractory disease, 74% were DLBCL NOS, and 26% were tDLBCL. Dose escalation from 50 to 450 x 106 cells with pem regimen A and B have been completed without DLTs. G . 3 treatment emergent AEs that occurred . 15% were neutropenia (89%), thrombocytopenia (58%), anemia (47%), febrile neutropenia (16%), and hypophosphataemia (16%). Across all dose levels, there were 0% sCRS with primary infusion and 5% severe neurotoxicity (sNT) (1/19), which resolved. There were no cases of sCRS and no neurotoxicity of any grade at . 50 x 106 cells. Eighteen patients were evaluable for efficacy. Among the 11 treated at dose . 50 x 106, the ORR and CRR were 64% and 55%, and all CRs are ongoing (1-12 mth). Two out of 3 patients achieved CR at 450 x 106 cells on pem regimen B. Additional patients and longer follow up, as well as biomarkers, will be presented. Conclusions: AUTO3 at . 50 x 106 CAR T cells with pembrolizumab induces CRs without severe CRS or neurotoxicities of any grade. Clinical trial information: NCT03287817. Research Sponsor: Autolus Therapeutics.

8002 Oral Abstract Session, Fri, 8:00 AM-11:00 AM

First-in-human data of ALLO-501 and ALLO-647 in relapsed/refractory large cell or follicular lymphoma (R/R LBCL/FL): ALPHA study.

Sattva Swarup Neelapu, Javier Munoz, Frederick Lundry Locke, David Bernard Miklos, Robert Brown, Jennifer T. McDevitt, Armen Mardiros, Eren Demirhan, Cyril Konto, Michael Timothy Tees; The University of Texas MD Anderson Cancer Center, Department of Lymphoma/Myeloma, Houston, TX; Banner MD Anderson Cancer Center, Gilbert, AZ; H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL; Stanford University School of Medicine, Stanford, CA; Allogene Therapeutics, South San Francisco, CA; Colorado Blood Cancer Institute/Sarah Cannon Research Institute, Denver, CO

Background: Allogeneic (off the shelf) chimeric antigen receptor (CAR) T cell therapy addresses the logistical challenges and variable product quality of autologous CAR T therapy. ALLO-501 is a genetically modified anti-CD19 CAR T cell product in which the TCR alpha constant gene is disrupted to reduce the risk of graft-versus-host disease (GvHD) and the CD52 gene is disrupted to permit the use of ALLO-647, an anti-CD52 mAb, for selective and prolonged host lymphodepletion. Methods: This is an open-label, Phase 1 trial (NCT03939026) in adults with R/R LBCL/FL who have received $ 2 prior lines of therapy; prior anti-CD19 cell therapy is allowed. Patients (pts) receive fludarabine (flu) 90 mg/m2, cyclophosphamide (cy) 900 mg/m2, and ALLO-647 39 or 90 mg followed by ALLO- 501 at 1 of 3 dose levels (DL) in a 3+3 design: 40, 120, and 360 3 106 CAR+ T cells. Results: As of 20 January 2020, 12 pts were enrolled: 9 received ALLO-501 at 3 DLs (4, 4 & 1 pts in DL1, DL2 and DL3 respectively), 1 pt discontinued due to kidney injury prior to lymphodepletion and 2 are starting treatment. Of the 9 treated pts aged 42 to 70 years: 5 had LBCL, 2 were female, 3 had primary refractory disease, and 3 had prior autologous stem cell transplants. The median number of prior lines of therapies was 3 (range 2 to 4). All treated pts received 39 mg of ALLO-647. No DLTs or GvHD have been observed to date. Most common Grade (Gr) $ 3 adverse events were neutropenia (55.6%), leukopenia (33.3%) and anemia (22.2%). Two pts (22.2%) developed cytokine release syndrome (1 Gr1 and 1 Gr2) that resolved within 72 hrs without steroids or tocilizumab. One pt developed Gr1 neurotoxicity that resolved without treatment. Infections included upper respiratory tract infection (Gr2), CMV (Gr3) and EBV viremia (Gr1), all reported in a single pt and resolved. One pt had a Gr2 infusion reaction to ALLO-647 which resolved with antihistamines. The overall response rate is 78% (95% exact CI: 40%, 97%): 3 complete and 4 partial responses. With a median follow up of 2.7 mos, 4 pts have ongoing responses and 3 pts progressed at 2, 4 and 6 mos. ALLO-501 cell expansion by qPCR was observed in 4 of 6 pts in varying degrees. Conclusions: These early data suggest that ALLO-501 and ALLO-647 have a manageable safety profile. ALLO-647 may be an effective and selective lympho- depleting agent with CD52 gene editing, and ALLO-501 shows evidence of clinical activity in pts with advanced NHL. Enrollment is ongoing, and updated safety, efficacy, PK/PD data will be presented including pts treated with increasing doses of ALLO-647. Clinical trial information: NCT03939026. Research Sponsor: Allogene Therapeutics.

8003 Oral Abstract Session, Fri, 8:00 AM-11:00 AM

Phase I study of the Bcl-2 inhibitor venetoclax with DA-EPOCH-R as initial therapy for aggressive B-cell lymphomas.

Sarah C. Rutherford, Jeremy S. Abramson, Nancy L. Bartlett, Stefan K. Barta, Nadia Khan, Robin Joyce, Kami J. Maddocks, Ying Yuan, Trisha Ali-Shaw, Silvia Senese, Jason Westin, John Paul Leonard; Weill Cornell Medicine, New York, NY; Massachusetts General Hospital Cancer Center; Harvard Medical School, Boston, MA; Washington University School of Medicine, Siteman Cancer Center, St. Louis, MO; Fox Chase Cancer Center, Philadelphia, PA; Beth Israel Deaconess Medical Center, Boston, MA; The Ohio State University Comprehensive Cancer Center, Columbus, OH; The University of Texas MD Anderson Cancer Center, Houston, TX; University of Texas MD Anderson Cancer Center, Houston, TX

Background: Dose-adjusted (DA) EPOCH-R is a frontline treatment for aggressive B-cell lymphomas. Bcl-2 is associated with chemoresistance due to BCL2 gene rearrangement or protein overexpression in lymphomas and is antagonized by BH3 mimetic venetoclax (ven). We conducted a phase I study combining ven with DA-EPOCH-R in aggressive B-cell lymphomas. Methods: This phase 1 study used Bayesian optimal interval design with dose expansion. Eligible patients (pts) were 18 years with newly diagnosed diffuse large B-cell (DLBCL), primary mediastinal, and high grade B-cell lymphoma (HGBCL) with double hit (DHL) or not otherwise specified (NOS). Ven was dosed at 400 mg (DL1), 600 mg (DL2), and 800 mg (DL3) daily for 10 days with 6 cycles of DA-EPOCH-R. A subsequent cohort received ven 600 mg daily for 5 days (DL2B). Toxicities were graded by CTCAE v4.0 and response assessed by Lugano criteria. Dose limiting toxicity (DLT) period was cycle 1 and primarily included grade (gr) $3 neutropenia on cycle 2 day 1, gr $4 febrile neutropenia/thrombocytopenia, and gr $3 nausea, vomiting, diarrhea despite supportive care. Results: 30 pts enrolled with median age 64 (24- 79), and 50% female. Ann Arbor stage was III-IV in 23. IPI was high risk in . 50%. Diagnosis was DHL (15), DLBCL NOS (13), and HGBCL NOS (2). 18 had MYC and 14 had BCL2 rearrangements. Bcl-2 was expressed $50% by IHC in 21/26 with data. There were no DLTs in DL1 (3 pts) or DL2 (9 pts). 1/6 had DLT in DL3 (gr 4 thrombocytopenia). Ven dose reductions occurred in subsequent cycles in 4 (2 in DL2; 2 in DL3). Of 18 in DL1-3, EPOCH was escalated above level 1 in 1 and de-escalated below level 1 in 7. Because of delays and ven dose reductions in DL2-3 due in part to cytopenias, infections and GI toxicities, we accrued DL2B. In DL2B, 0/12 pts had DLTs or ven dose reductions. EPOCH was escalated above level 1 in 4 and de-escalated below level 1 in 3. 1 died of sepsis during cycle 3. Most common gr 3-4 toxicities across all dose levels were cytopenias; febrile neutropenia occurred in 57%. Most common non-hematologic toxicities of all grades were hypocalcemia, nausea, diarrhea, hypokalemia and fatigue. ORR (N = 30) ITT was 97% with 27 (90%) complete and 2 (7%) partial responses; 1 was not evaluable. Follow up is ongoing. Of 15 DHL, ORR and CRR were 93% and 80%. Conclusions: We identified ven 600 mg for 5 days per cycle as RP2D with DA-EPOCH-R. DL2B was well tolerated and required no ven dose reductions. Further efficacy and safety is being evaluated in Alliance 51701, DA- EPOCH-R/R-CHOP in DH/double expressor lymphomas, using the dosing regimen defined by this study. Clinical trial information: NCT03036904. Research Sponsor: Genentech.

8004 Oral Abstract Session, Fri, 8:00 AM-11:00 AM

A multicenter phase II study of venetoclax plus dose-adjusted R-EPOCH (VR-EPOCH) for Richter’s syndrome.

Matthew Steven Davids, Kerry Anne Rogers, Svitlana Tyekucheva, Samantha Pazienza, Sarah K Renner, Josie Montegaard, Michael Rocchio, Udochukwu Ihuoma, Caron A. Jacobson, David Christopher Fisher, Jennifer R. Brown, Philip A. Thompson; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA; Division of Hematology, The Ohio State University, Columbus, OH; Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Medical Oncology, Dana–Farber Cancer Institute, Boston, MA; Dana-Farber Cancer Institute, Boston, MA

Background: While therapeutic options for CLL have improved, patients (pts) who develop Richter’s Syndrome (RS) still have a poor prognosis. Chemoimmunotherapy regimens such as R-EPOCH lead to CR in about 20% of RS pts, but PFS/OS is typically , 6 mo. The oral Bcl-2 inhibitor venetoclax (ven) had a 43% single agent response rate in RS. Here, we report the results of a phase 2 study of VR-EPOCH in RS. Methods: This is a single-arm, phase 2, IST of VR-EPOCH for RS (NCT03054896) at 3 US sites. CLL pts with biopsy-confirmed DLBCL were treated with R-EPOCH for 1 cycle, then after count recovery underwent accelerated inpatient ven daily ramp-up (20/50/100/200/400 mg), then ven + R-EPOCH for up to 5 more 21d cycles (ven 400 mg qd, d1-10 each cycle). Responders went to alloHCT or to continuous daily ven 400 mg maintenance. Response evaluation by Lugano criteria with PET/CT. Results: As of the data cut on 2/3/2020, the study is fully enrolled with 27 pts. Median age: 63 yrs (range 49-77). CLL features: 26% del(17p); 44% complex karyotype; 48% IGHV unmutated; 41% TP53 and 15% NOTCH1 mutation. Median prior CLL treatments: 2 (range 0-5, prior ibrutinib [n = 8], ven [n = 2], and PI3Ki [n = 2]) with 6 untreated CLL pts. Median # ven + R-EPOCH cycles: 4 (range 0-6). 5 pts had dose de-escalation of R-EPOCH, 1 pt had dose escalation. $Gr 3 heme tox: neutropenia (58%), anemia (50%), thrombocytopenia (50%). $Gr 3 non-heme tox in . 15% of pts: febrile neutropenia (38%) and hypophosphatemia (23% each). No pts had TLS with daily ven ramp-up. Infections: pneumonia (n = 4), sepsis during C1 of R-EPOCH prior to starting ven (n = 3), enterocolitis (n = 3), sinusitis (n = 2), and 1 pt each with influenza A and norovirus. 10 pts have died, including 7 due to disease progression (2 during C1 before ven), and 1 each due to sepsis, sudden death, and GVHD post-alloHCT. In ITT analysis, 16 responded (ORR 59%); 13/27 (48%) had CR as best response, all with undetectable bone marrow MRD for CLL. Six pts were not evaluable for efficacy of the combo (5 had toxicity in C1 and never started ven, 1 withdrew after C1). In the 21 pts who started combo therapy, the ORR was 76%, CR rate 62%. Only 1 pt with CR has progressed. The pt on longest ven maintenance is in CR 2 years post chemo. 8 pts went to alloHCT, with pts still in CR now up to 2.5 yrs post-alloHCT. With a median follow-up of 9.3 mo (range 0.6-30), median PFS and OS are both 16.3 mo. Conclusions: VR-EPOCH is active for RS. Expected toxicities from intensive chemoimmunotherapy and ven were seen, but daily ven ramp-up was feasible. The 48% CR rate and median PFS of 16.3 mo are favorable in the context of historical results. Clinical trial information: NCT03054896. Research Sponsor: Genentech, Other Foundation.

8005 Oral Abstract Session, Fri, 8:00 AM-11:00 AM

KEYNOTE-204: Randomized, open-label, phase III study of pembrolizumab (pembro) versus brentuximab vedotin (BV) in relapsed or refractory classic Hodgkin lymphoma (R/R cHL).

John Kuruvilla, Radhakrishnan Ramchandren, Armando Santoro, Ewa Paszkiewicz-Kozik, Robin Gasiorowski, Nathalie Johnson, Vladimir Melnichenko, Laura Maria Fogliatto, Iara Goncalves, Jose de Oliveira, Valeria Buccheri, Guilherme Fleury Perini, Neta Goldschmidt, Sergey Alekseev, Iryna Kryachok, Naohiro Sekiguchi, Ying Zhu, Akash Nahar, Patricia Marinello, Pier Luigi Zinzani; Princess Margaret Cancer Centre, Toronto, ON, Canada; University of Tennessee, Knoxville, TN; Humanitas Clinical and Research Center, IRCCS, Rozzano, Italy; Maria Sklodowska-Curie Institute of Oncology, Warsaw, Poland; Concord Repatriation General Hospital, University of Sydney, Sydney, Australia; Jewish General Hospital, Montreal, QC, Canada; Pirogov National Medical and Surgical Center, Moscow, Russian Federation; Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil; Fundacao Pio XII-Hospital de Cancer,ˆ S~ao Paulo, Brazil; Casa de Saude Santa Marcelina, S~ao Paulo, Brazil; Hospital das Clı´nicas da Faculdade de Medicina da Universidade de S~ao Paulo, S~ao Paulo, Brazil; Hospital Israelita Albert Einstein, S~ao Paulo, Brazil; Hadassah Medical Center, Jersusalem, Israel; N.N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russian Federation; National Cancer Institute, Kiev, Ukraine; National Hospital Organization Disaster Medical Center, Tokyo, Japan; Merck & Co., Inc., Kenilworth, NJ; Institute of Hematology “L. e A. Ser`agnoli”, University of Bologna, Bologna, Italy

Background: PD-1 blockade via pembro monotherapy showed antitumor activity in R/R cHL. KEYNOTE- 204 (NCT02684292) was a randomized, international, open-label, phase III study of pembro vs BV in R/R cHL. Methods: Patients (pts) were aged $18 y, were post2autologous stem cell transplant (auto- SCT) or ineligible for auto-SCT, and had measurable disease and ECOG PS 0 or 1. BV-naive and BV- exposed pts were eligible. Pts were randomized 1:1 to pembro 200 mg IV Q3W or BV 1.8 mg/kg IV Q3W and stratified by prior auto-SCT (yes vs no) and status after 1L therapy (primary refractory vs relapsed ,12 mo vs relapsed $12 mo after end of 1L therapy). Primary end points: PFS by blinded independent central review (BICR) per International Working Group (IWG) criteria including clinical and imaging data after auto-SCT or allogeneic SCT (allo-SCT) and OS. Key secondary end points: PFS excluding clinical and imaging data after auto-SCT or allo-SCT (PFS-secondary), and ORR by BICR per IWG, PFS by investigator review per IWG, and safety. Exploratory end point: DOR by BICR per IWG. Results: 304 pts were randomized and 300 were treated (148, pembro; 152, BV); 256 discontinued. Median (range) follow-up: 24.7 (0.6-42.3) mo. 15 pts were BV exposed. Median (range) time on treatment was 305.0 (1-814) and 146.5 (1-794) days with pembro and BV, respectively. Statistically significant improvement was observed with pembro vs BV for primary PFS analysis (HR 0.65 [95% CI 0.48-0.88; P =0.00271]; median 13.2 vs 8.3 mo); 12-mo PFS rates were 53.9% vs 35.6%, respectively. Benefit was observed in all subgroups tested, including pts with no auto-SCT (HR=0.61), primary refractory disease (HR=0.52), prior BV (HR=0.34) and BV naive (HR=0.67). Significant improvement in PFS-secondary was observed with pembro vs BV (HR 0.62 [95% CI 0.46- 0.85]; median 12.6 vs 8.2 mo). Per investigator assessment, PFS was longer with pembro vs BV (HR 0.49 [95% CI 0.36-0.67]; median 19.2 vs 8.2 mo). ORR was 65.6% for pembro and 54.2% for BV; CR rates were 24.5% and 24.2%, respectively. Median (range) DOR was 20.7 mo (0.0+ to 33.2+) for pembro and 13.8 mo (0.0+ to 33.9+) for BV. Grade 3-5 TRAEs: 19.6% of pts with pembro and 25.0% with BV. One death due to TRAE occurred with pembro (pneumonia). Conclusions: In pts with R/R cHL, pembro was superior to BV and demonstrated statistically significant and clinically meaningful improvement in PFS across all subgroups, with safety consistent with previous reports. Pembro monotherapy should be standard of care for this pt population with R/R/cHL. Clinical trial information: NCT02684292. Research Sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

8006 Oral Abstract Session, Fri, 8:00 AM-11:00 AM

Initial results of a multicenter, investigator initiated study of MRD driven time limited therapy with zanubrutinib, obinutuzumab, and venetoclax.

Jacob Drobnyk Soumerai, Anthony R. Mato, Jason Carter, Ahmet Dogan, Ephraim Hochberg, Jeffrey A. Barnes, Audrey M. Hamilton, Jeremy S. Abramson, Connie Lee Batlevi, Erel Joffe, Matthew J. Matasar, Ariela Noy, Colette Ngozi Owens, Maria Lia Palomba, Tak Takvorian, Kelsey Flaherty, Lauren Ramos, Lindsey Elizabeth Roeker, Omar Ibrahim Abdel-Wahab, Andrew David Zelenetz; Massachusetts General Hospital Cancer Center; Harvard Medical School, Boston, MA; Memorial Sloan Kettering Cancer Center, New York, NY; Memorial Sloan Kettering Cancer Center, Basking Ridge, NJ; Massachusetts General Hospital Cancer Center, Boston, MA

Background: Venetoclax (Ven)-Obinutuzumab (O) is approved for chronic lymphocytic leukemia (CLL) achieving frequent undetectable minimum residual disease (uMRD; Fischer NEJM 2019). Ven- Ibrutinib is synergistic with frequent uMRD but with grade .3 neutropenia in 33-48% patients (pts; Tam ASH 2019; Jain NEJM 2019). Zanubrutinib (B) is a highly specific BTK inhibitor that demonstrated 100% occupancy in lymphoid tissues, so may be preferred to combine with OVen. We hypothesize that treatment (tx) with BOVen using an MRD driven discontinuation strategy will achieve frequent uMRD and durable responses. Methods: In this multicenter, investigator initiated phase 2 trial (NCT03824483), eligible pts had previously untreated CLL requiring tx per iwCLL, ECOG PS ,2, ANC .1, PLT .75 (ANC .0, PLT .20 if due to CLL). BOVen was administered in 28D cycles: B 160 mg PO BID starting D1; O 1000 mg IV D1 or split D1-2, 8, 15 of C1, D1 of C2-8; Ven ramp up initiated C3D1 (target 400 mg QD). Tx duration was determined by a prespecified uMRD endpoint (min 8 cycles). MRD was assessed in peripheral blood (PB; flow cytometry, sensitivity .1024) starting C7D1 then every 2 cycles. Once PB uMRD was determined and confirmed in bone marrow (BM), tx continued 2 additional cycles. Adverse events (AE) were assessed per CTCAE v5. Median (med) time to uMRD (primary endpoint) was estimated using the Kaplan-Meier method. Results: The study accrued 39 pts (3-10/19): med age 59 years (23-73), 3:1 male, CLL IPI .4 26/39 (67%), unmutated IGHV 28/39 (72%), 17p del/TP53 mutated 4/39 (10%), all pts were evaluable for toxicity with 37 evaluable for efficacy. At a med follow up of 8 months (mo; 3-10), 25/37 (68%) pts achieved PB uMRD. Med time to PB uMRD is 6 mo (4-8+). Another 8/37 (22%) had PB MRD , 0.1%. Of 25 with PB uMRD, 19 had BM uMRD with 10/19 completing 2 additional cycles and discontinued; 3 had BM MRD (all ,0.02%); 3 pending. The most common tx emergent AEs were neutropenia (49%), infusion related reaction (41%), bruising (39%), and diarrhea (39%). Grade $3 AEs in $5% pts were neutropenia (13%), thrombocytopenia (5%), rash (5%), and pneumonia (5%). Of 17 pts at high risk for TLS on C1D1, 2 cycles of BO reduced TLS risk to low/medium at Ven initiation in 15 (88%). No pts had laboratory/clinical TLS (Howard). Conclusions: BOVen is well tolerated and achieves rapid uMRD: currently 68% PB uMRD and 51% BM uMRD with limited follow up (to be updated on presentation). Ten (27%) have discontinued treatment thus far. The value of MRD directed treatment duration will be evaluated with continued follow up. Clinical trial information: NCT03824483. Research Sponsor: BeiGene; Genentech/Roche, Other Foundation, Lymphoma Research Fund (Andrew Zelenetz)).

8007 Oral Abstract Session, Fri, 8:00 AM-11:00 AM

ASPEN: Results of a phase III randomized trial of zanubrutinib versus ibrutinib for patients with Waldenstr¨om macroglobulinemia (WM).

Constantine Si Lun Tam, Stephen Opat, Shirley D’Sa, Wojciech Jurczak, Hui-Peng Lee, Gavin Cull, Roger G. Owen, Paula Marlton, Bjorn E. Wahlin, Alessandra Tedeschi, Jorge J. Castillo, Tanya Siddiqi, Christian Buske, Veronique Leblond, Wai Y. Chan, Jingjing Schneider, Sunhee K. Ro, Aileen Cohen, Jane Huang, Meletios A. Dimopoulos; Peter MacCallum Cancer Centre, Melbourne, St Vincent’s Hospital, Fitzroy, University of Melbourne, Parkville and Royal Melbourne Hospital, Parkville, Victoria, Australia; Monash Health, Monash University, Clayton, Victoria, Australia; University College London Hospital Foundation Trust, London, United Kingdom; Maria Sklodowska-Curie National Institute of Oncology, Krakow, Poland; Flinders Medical Centre, Adelaide, SA, Australia; Sir Charles Gairdner Hospital and University of Western Australia, Perth, WA, Australia; St. James’s University Hospital, Leeds, United Kingdom; Princess Alexandra Hospital and University of Queensland, Brisbane, Queensland, Australia; Karolinska Universitetssjukhuset and Karolinska Institutet, Stockholm, Swe- den; ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA; City of Hope National Medical Center, Duarte, CA; CCC Ulm- Universitatsklinikum ¨ Ulm, Baden-Wurttemberg, ¨ Germany; Sorbonne University, Pitie ´ Salpetriˆ ere ` Hospital, Paris, France; BeiGene USA, Inc., San Mateo, CA; National and Kapodistrian University of Athens, Athens, Greece

Background: Bruton tyrosine kinase (BTK) inhibition is an emerging standard of care for WM. ASPEN is a randomized phase 3 study comparing zanubrutinib (ZANU), a potent and selective BTK inhibitor, versus ibrutinib (IBR), a first generation BTK inhibitor, in WM patients. Methods: Patients with WM and MYD88 mutation were randomly assigned 1:1 to receive ZANU (160 mg twice daily) or IBR (420 mg once daily). Patients without MYD88 mutations were assigned to a separate cohort, received ZANU, and are reported separately. Randomization was stratified by CXCR4 mutational status and the number of lines of prior therapy (0 vs 1-3 vs .3). The primary end point was the proportion of patients achieving a complete response or very good partial response (CR+VGPR). Sample size was calculated to provide 81% power to detect a difference in CR+VGPR rate of 35% vs 15% in the subset of patients with relapsed or refractory (R/R) WM. Primary analysis was planned to occur at ~12 months after last patient enrolled. Results: In total, 201 patients were randomized from Jan 2017 to Jul 2018. The treatment groups were well balanced for important baseline factors, except in the ZANU arm there were more elderly patients (aged .75 years, 33.3% vs 22.2%) and more anemia (hemoglobin #110 g/L, 65.7% vs 53.5%). At a median follow-up of 19.4 months, the rate of CR+VGPR was 28.4% vs 19.2% with ZANU vs IBR, respectively (2-sided P=0.09). Rates of atrial fibrillation, contusion, diarrhea, edema peripheral, hemorrhage, muscle spasms, pneumonia, and adverse events (AEs) leading to discontinuation or death were lower with ZANU. The rate of neutropenia was higher with ZANU (Table); however, grade $ 3 infection rates were similar (17.8% vs 19.4%). Conclusions: ASPEN is the largest phase 3 trial of BTK inhibitors in WM and the first head-to-head comparison of BTK inhibitors in any disease. Although not statistically significant, ZANU was associated with a higher CR+VGPR response rate, and demonstrated clinically meaningful advantages in safety and tolerability compared to IBR. Clinical trial information: NCT03053440. Research Sponsor: BeiGene.

ZANU IBR Assessment, % (n=102) (n=99) CR+VGPR Rate 28.4 19.2 12-mo PFS/OS – overall population 89.7/97.0 87.2/93.9 12-mo PFS/OS – R/R population (n=83 vs 81) 92.4/98.8 85.9/92.5 AEs ‡Grade 3 / Grade 5 58.4 /1.0 63.3/4.1 AEs leading to discontinuation 4.0 9.2 Atrial fibrillation/flutter 2.0 15.3 Hypertension 10.9 17.3 Major bleedinga 5.9 9.2 Neutropenia 29.7 13.3 PFS/OS, progression-free survival/overall survival. aIncludes grade $3 hemorrhage and central nervous system bleeding of any grade.

8008 Oral Abstract Session, Fri, 8:00 AM-11:00 AM

Interim analysis of ZUMA-5: A phase II study of axicabtagene ciloleucel (axi-cel) in patients (pts) with relapsed/refractory indolent non-Hodgkin lymphoma (R/R iNHL).

Caron A. Jacobson, Julio C. Chavez, Alison R. Sehgal, Basem M. William, Javier Munoz, Gilles A. Salles, Carla Casulo, Pashna N. Munshi, David G. Maloney, Sven De Vos, Ran Reshef, Lori A. Leslie, Ibrahim Yakoub-Agha, Olalekan O. Oluwole, Henry C. Fung, Vicki Plaks, Yin Yang, Jennifer Lee, Mauro P. Avanzi, Sattva Swarup Neelapu; Dana-Farber Cancer Institute, Boston, MA; H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL; UPMC Hillman Cancer Center, Pittsburgh, PA; The Ohio State University Comprehensive Cancer Center, Columbus, OH; Banner MD Anderson Cancer Center, Gilbert, AZ; Centre Hospitalier Lyon Sud, Pierre Benite, ´ France; University of Rochester Medical Center-James P. Wilmot Cancer Center, Rochester, NY; Georgetown Lombardi Comprehensive Cancer Center, Washington, DC; Fred Hutchinson Cancer Research Center, Seattle, WA; Ronald Reagan University of California Los Angeles Medical Center, Santa Monica, CA; Columbia University Herbert Irving Comprehensive Cancer Center, New York City, NY; John Theurer Cancer Center, Hackensack, NJ; Centre Hospitalier Regional ´ Universitaire de Lille, Lille, France; Vanderbilt University Medical Center, Nashville, TN; Fox Chase Cancer Center, Philadelphia, PA; Kite, a Gilead Company, Santa Monica, CA; The University of Texas MD Anderson Cancer Center, Department of Lymphoma/ Myeloma, Houston, TX

Background: Advanced stage iNHL, including follicular lymphoma (FL) and marginal zone lymphoma (MZL), is considered incurable as most pts experience multiple relapses (Wang, et al. Ther Adv Hematol. 2017), highlighting a need for novel therapies. Here, we present interim results from ZUMA- 5, a Phase 2, multicenter study of axi-cel, an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy, in pts with R/R iNHL. Methods: Adults with R/R FL (Grades 1-3a) or MZL (nodal or extranodal) after $ 2 lines of therapy (including an anti-CD20 monoclonal antibody [mAb] with an alkylating agent), and an ECOG of 0 – 1 were eligible. Pts were leukapheresed and received conditioning chemotherapy followed by axi-cel infusion at 2 3 106 CAR T cells/kg. The primary endpoint was objective response rate (ORR) by central review (Cheson, et al. J Clin Oncol. 2014). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety, and blood levels of cytokines and CAR T cells. Results: As of 8/20/19, 94 pts (80 FL; 14 MZL) received axi-cel with a median follow-up of 11.5 mo (range, 4.2 – 24.9). Median age was 63 y (range, 34 – 79), 47% of pts were male, 52% had stage IV disease, 51% had $ 3 FLIPI, and 59% had high tumor bulk (GELF). Pts had a median 3 prior lines of therapy, 66% progressed , 2 y after initial anti- CD20 mAb-containing therapy (POD24), and 73% were refractory to the last prior treatment. Of 87 pts evaluable for efficacy, ORR was 94% (79% complete response [CR] rate). Pts with FL (n = 80) had an ORR of 95% (80% CR rate). Pts with MZL (n = 7) had an ORR of 86% (71% CR rate). Overall, 68% of pts had ongoing responses as of the data cutoff. Updated data, including DOR, PFS, and OS with longer follow-up, will be included in the presentation. Of 94 pts evaluable for safety, 83% experienced Grade $ 3 adverse events (AEs), most commonly neutropenia (33%) and anemia (28%). Grade $ 3 cytokine release syndrome (CRS; per Lee et al, Blood 2014) and neurologic events (NEs; per CTCAE v4.03) occurred in 11% and 19% of pts, respectively. Median times to onset of CRS and NEs were 4 and 7 d, with median durations of 6 and 14.5 d. There were 2 Grade 5 AEs: multisystem organ failure in the context of CRS (related to axi-cel) and aortic dissection (unrelated to axi-cel). Median peak and AUC0-28 CAR T cell levels were 44 cells/mL and 490 cells/mL 3 d, respectively. Conclusions: Axi-cel demonstrated significant and durable clinical benefit, with high rates of ORR and CR, and a manageable safety profile in pts with R/R iNHL. Clinical trial information: NCT03105336. Research Sponsor: Kite, a Gilead Company.

8009 Poster Discussion Session; Displayed in Poster Session (Board #342), Fri, 8:00 AM-11:00 AM, Discussed in Poster Discussion Session, Fri, 8:00 AM-11:00 AM

Epcoritamab (GEN3013; DuoBody-CD33CD20) to induce complete response in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL): Complete dose escalation data and efficacy results from a phase I/II trial.

Martin Hutchings, Pieternella Lugtenburg, Rogier Mous, Michael Roost Clausen, Martine Chamuleau, Kim Linton, Simon Rule, Juanita Suzanne Lopez, Roberto S Oliveri, Dena DeMarco, Brian Elliott, Peter Johnson; Rigshospitalet, Copenhagen, Denmark; Erasmus MC Cancer Institute, Department of Hematology, Rotterdam, Netherlands; Universitair Medisch Centrum Utrecht, Utrecht, Netherlands; Vejle Hospital, Vejle, Denmark; VU University Medical Center, Amsterdam, Netherlands; The Christie NHS Foundation Trust, Manchester, United Kingdom; Plymouth University Medical School, Plymouth, United Kingdom; The Royal Marsden Hospital, London, United Kingdom; Genmab A/S, Copenhagen, Denmark; Genmab, Princeton, NJ; Cancer Research UK Centre, Southampton, United Kingdom

Background: CD33CD20 bispecific antibodies (bsAbs) have demonstrated promising results for the treatment of pts with R/R B-NHL. Epcoritamab is a novel subcutaneously administered bsAb with a favorable safety profile and encouraging preliminary anti-tumor activity at low doses in both aggressive and indolent B-NHL. Here we present updated safety and efficacy data from the ongoing trial (NCT03625037). Methods: Adults with R/R CD20+ B-NHL received a single SC injection of flat- dose epcoritamab in 28-day cycles (q1w: cycle 1–2; q2w: cycle 3–6; q4w thereafter) until disease progression or unacceptable toxicity. Primary objectives are determination of maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Secondary objectives include anti-tumor activity. Results: As of 8 Jan 2020, 41 pts with median age of 66 (range: 21–82) were enrolled. Most pts had DLBCL/HGBCL (73%) or FL (20%) and received a median (range) of 3 (1–6) and 5 (2–18) prior lines of treatment. No DLTs were observed (median follow-up: 4.7 mo; range: 3.7– 5.6). MTD has not been reached. Most common TEAEs (.35%) were pyrexia (71%), fatigue (46%), and injection site reaction (39%; all Gr 1). AEs of special interest included cytokine release syndrome (59%; all Gr 1/2; all resolved) and cytokine release-related decreased CARTOX-10 score (n=1). There was no clinical tumor lysis syndrome or treatment-related deaths. Treatment is ongoing in 13 pts. Anti-tumor activity was observed at minimal efficacy threshold (based on PK modelling) for DLBCL/HGBCL and FL (Table). Complete dose escalation data and RP2D will be presented. Conclusions: SC epcoritamab continues to demonstrate a favorable safety profile across all doses with no $Gr 3 CRS and no DLTs. Dose escalation data show improved efficacy as doses reach above the modeled predicted exposure threshold, inducing CRs in heavily pretreated DLBCL pts. All pts achieving CRs remain in remission. Clinical trial information: NCT03625037. Research Sponsor: Genmab.

Anti-tumor activity in R/R B-NHL. DLBCL/HGBCL ‡6 mg (n=12) FL ‡0.76 mg (n=7) Evaluable pts 96 ORR, n(%) CR 5 (56%) 4 (44%) 6 (100%) 0 PR 1 (11%) 6 (100%) SD 2 (22%) 0 PD 2 (22%) 0 Data snapshot 02112020

8011 Poster Discussion Session; Displayed in Poster Session (Board #344), Fri, 8:00 AM-11:00 AM, Discussed in Poster Discussion Session, Fri, 8:00 AM-11:00 AM

Prognostic impact of dose, duration, and timing of corticosteroid therapy in patients with large B-cell lymphoma treated with standard of care axicabtagene ciloleucel (Axi-cel).

Paolo Strati, fateeha furqan, Jason Westin, Luis Fayad, Sairah Ahmed, Hun Ju Lee, Swaminathan Padmanabhan Iyer, Ranjit Nair, Loretta J. Nastoupil, Simrit Parmar, Maria Alma Rodriguez, Felipe Samaniego, Raphael Steiner, Michael Wang, Chelsea Camille Pinnix, Christopher Flowers, Sandra B. Horowitz, Catherine Classen, Haleigh Mistry, Sattva Swarup Neelapu; The University of Texas MD Anderson Cancer Center, Department of Lymphoma/Myeloma, Houston, TX; Rochester General Hospital, Rochester, NY; The University of Texas MD Anderson Cancer Center, Houston, TX; Lehigh Valley Health Network, Allentown, PA; University of Texas, MD Anderson Cancer Center, Houston, TX; The University of Texas MD Anderson Cancer Center, Department of Radiation Oncology, Houston, TX; Emory University, Winship Cancer Institute, Atlanta, GA; University of Texas MD Anderson Cancer Center, Houston, TX

Background: Corticosteroids are commonly used for management of severe toxicities associated with chimeric antigen receptor (CAR) T-cell therapy. However, it remains unclear whether the dose, duration, and timing of corticosteroid therapy may impact clinical efficacy of CAR T-cell therapy. Methods: This is a retrospective analysis of patients with relapsed or refractory LBCL treated with standard of care axi-cel at MD Anderson Cancer Center, Houston, Texas between 01/2018 and 05/ 2019 (data cut-off 12/21/2019). Progression-free survival (PFS) was defined as time from axi-cel infusion to progression/death or last follow-up, and the Breslow test was used for comparisons between subgroups. Results: One hundred patients with relapsed or refractory LBCL were included in the study, and 60 (60%) received corticosteroids for management of toxicities after axi-cel infusion. There was no significant difference in baseline tumor burden, disease stage or international prognostic index between the 2 groups. The median cumulative dexamethasone-equivalent dose was 186 mg (range, 8-1803 mg) and the median duration of corticosteroid treatment was 9 days (range 1-30); 45 (45%) patients started corticosteroid treatment between day 0 and 7, and 15 (15%) beyond day 7. After a median follow-up of 10 months (95% CI 8-10 months), median PFS was 8 months (95% CI, 3-13 months), and use of corticosteroids (any dose) showed a trend for association with shorter PFS (6 vs 9 months, p = 0.13). Use of high-dose corticosteroids (Quartiles (Q) 3-4, 195-1803 mg) significantly associated with shorter PFS (2 vs 9 months, p = 0.005). A trend for shorter PFS was observed among patients receiving corticosteroids for a prolonged time (Q3-Q4, 10-30 days) (5 vs 8 months, p = 0.12) and among patients starting corticosteroids within the first 7 days after axi-cel infusion (6 vs 11 months, p = 0.07). At most recent follow-up, 36 patients died, 28 of progression. Median overall survival has not been reached, and was significantly shorter among patients who received corticosteroids (13 vs not reached, p = 0.006). Conclusions: Early and prolonged use of high- dose corticosteroids is associated with early progression and death in patients with LBCL treated with axi-cel. Additional evaluation is needed to understand the mechanism underlying this association. Research Sponsor: U.S. National Institutes of Health, Other Foundation.

8012 Poster Discussion Session; Displayed in Poster Session (Board #345), Fri, 8:00 AM-11:00 AM, Discussed in Poster Discussion Session, Fri, 8:00 AM-11:00 AM

Retreatment (reTx) of patients (pts) with refractory large B-cell lymphoma with axicabtagene ciloleucel (axi-cel) in ZUMA-1.

Frederick Lundry Locke, Nancy L. Bartlett, Caron A. Jacobson, Olalekan O. Oluwole, Javier Munoz, Lazaros J. Lekakis, Max S. Topp, Irit Avivi, Jenny J. Kim, Rong Chu, Lianqing Zheng, John M. Rossi, Adrian Bot, Sattva Swarup Neelapu; H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL; Washington University School of Medicine and Siteman Cancer Center, St Louis, MO; Dana-Farber Cancer Institute, Boston, MA; Vanderbilt University Medical Center, Nashville, TN; Banner MD Anderson Cancer Center, Gilbert, AZ; University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL; Medizinische Klinik und Poliklinik II, Universitatsklinikum ¨ Wurzburg, ¨ Wurzburg, ¨ Germany; Sourasky Medical Center, Tel Aviv, Israel; Kite, a Gilead Company, Santa Monica, CA; The University of Texas MD Anderson Cancer Center, Houston, TX

Background: Axi-cel, an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy, is approved in the US and EU for pts with relapsed/refractory large B cell lymphoma after $ 2 prior therapies. In the ZUMA-1 pivotal study (NCT02348216), the objective response rate (ORR) was 83% (58% complete response [CR] rate; Locke et al. Lancet Oncol. 2019). While axi-cel has demonstrated durable responses in a subset of pts, approximately half of all responders relapsed, and little is known on the viability of reTx with CAR T cell therapy. Here we report outcomes of pts retreated with axi-cel in ZUMA-1. Methods: Pts with progressive disease (PD) were eligible for reTx if there was no evidence of CD19 loss by local review, and if during 1st Tx they did not experience any dose-limiting toxicities, as defined in Phase 1, or comparable toxicities in Phase 2. Pts received the same regimen at reTx as at 1st Tx: 2 3 106 CAR T cells/kg after conditioning chemotherapy. Results: Thirteen pts in Cohorts 1 – 4 received axi-cel reTx. Prior to 1st Tx, most pts (69%) had an IPI score 3-4, 85% had disease stage 3-4, and the median number of prior regimens was 3 (range, 2 – 6). At first Tx, 6 pts achieved a CR, 6 achieved partial response (PR), and 1 pt had stable disease (SD) prior to PD. Median duration of first response was 96 days (range, 56 – 274). There was no Grade $ 3 cytokine release syndrome (CRS; 6 pts each had Grade 1 and 2). There were no Grade 4 or 5 neurologic events (NEs; 2 pts had Grade 1, 1 had Grade 2, and 7 had Grade 3). Upon reTx, 54% of pts achieved response (4 CR, 3 PR). Response to reTx was more common among pts who achieved CR at 1st Tx (83%; 4/6 CR, 1 PR, 1 SD) than in pts who achieved PR at 1st Tx (33%; 2/6 PR, 1 SD, 3 PD), and no response was observed in the pt with SD at 1st Tx. Median duration of response at reTx was 81 days (range, 1 – 225+). Response with reTx was longer than that with 1st Tx for 2 pts. One pt remains in response 255 days post-reTx. Comparable rates of CRS were observed with reTx as with 1st Tx. Compared with 1st Tx, fewer pts experienced NEs with reTx, and those that did occur were of lower grade: 23% (3 of 13 pts) had Grade 3; 23% (3 of 13 pts) had Grade 1, and 8% (1 of 13 pts) had Grade 2. Peak CAR T cell expansion was lower upon reTx vs 1st Tx (median, 4.3 vs 66.1 CAR gene-marked cells/mL blood). Conclusions: Based on this limited sample size, reTx with axi-cel may have clinical efficacy, although transient, in some pts, especially those who achieve CR with 1st Tx. CAR T cell expansion and severe CRS and NEs may be attenuated at reTx. Further studies with additional pts are needed to confirm these results. Clinical trial information: NCT02348216. Research Sponsor: Kite, a Gilead Company.

8013 Poster Discussion Session; Displayed in Poster Session (Board #346), Fri, 8:00 AM-11:00 AM, Discussed in Poster Discussion Session, Fri, 8:00 AM-11:00 AM

Nivolumab and brentuximab vedotin (BV)-based, response-adapted treatment in children, adolescents, and young adults (CAYA) with standard-risk relapsed/refractory classical Hodgkin lymphoma (R/R cHL): Primary analysis.

Peter D. Cole, Christine Mauz-Korholz, ¨ Maurizio Mascarin, Gerard ´ Michel, Stacy Cooper, Auke Beishuizen, Kasey J. Leger, Loredana Amoroso, Salvatore Buffardi, Charlotte Rigaud, Markus Puhlmann, Stephen Francis, Mariana Sacchi, Richard A. Drachtman, Paul David Harker- Murray, Thierry Leblanc, Stephen Daw, Kara M. Kelly; Rutger’s Cancer Institute of New Jersey, New Brunswick, NJ; University Hospital Justus Liebig University, Giessen and Medical Faculty of the Martin Luther University Halle-Wittenberg, Halle, Germany; IRCCS Centro di Riferimento Oncologico, Aviano, Italy; Hopitalˆ de la Timone, Marseilles, France; Johns Hopkins Hospital, Baltimore, MD; Princess Maxima ´ Center for Pediatric Oncology, Utrecht, Netherlands; Seattle Children’s Hospital, Seattle, WA; IRCCS Istituto Giannina Gaslini, Genoa, Italy; Santobono-Pausilipon Hospital, Naples, Italy; Gustave Roussy Cancer Campus, Villejuif, France; Seattle Genetics, Bothell, WA; Bristol-Myers Squibb, Princeton, NJ; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Children’s Hospital of Wisconsin, Milwaukee, WI; Hopitalˆ Robert-Debr´e APHP, Paris, France; University College Hospital, London, United Kingdom; Roswell Park Comprehensive Cancer Center, Buffalo, NY

Background: Outcomes for younger patients (pts) with R/R cHL are poor, particularly for those without complete metabolic response (CMR) before autologous transplant (auto-HCT). Nivolumab + BV has shown 67% CMR and a high 2-y PFS rate as first salvage in adults with R/R cHL. CheckMate 744 (NCT02927769) is an ongoing phase 2 study for CAYA with R/R cHL, evaluating a risk-stratified, response-adapted approach using nivolumab + BV and, for pts without CMR, BV + bendamustine. In the initial analysis of the standard-risk cohort (R2), the regimen was well tolerated with high CMR rates before consolidation with high-dose chemotherapy plus auto-HCT. We report data from the primary analysis. Methods: Pts were aged 5–30 y and had first-line treatment (tx) without auto-HCT. Risk stratification has been described previously (Harker-Murray, ASH 2018). Pts received 4 induction cycles of nivolumab + BV; pts without CMR by blinded independent central review (BICR) received BV + bendamustine intensification. Pts with CMR at any time could proceed to consolidation off study. Response was per Lugano 2014 criteria. Primary endpoint: CMR rate (Deauville #3) per BICR any time before consolidation. Results: At database lock, 44 pts were treated in R2 (median follow up: 20.9 mo); 43 received 4 induction cycles and 11 received intensification. Median age was 16 y (range 9–30); 24 (55%) pts had primary refractory cHL and 20 had relapsed cHL. CMR rates and ORR any time before consolidation and after induction are shown in Table. 1-y PFS rate by BICR was 91% (90% CI 77–96). During induction, 8 (18%) pts experienced grade (G) 3–4 tx-related adverse events (TRAEs); the most common any grade TRAEs were nausea and hypersensitivity (20% each). 1 TRAE led to discontinuation (G3 anaphylaxis). Most tx-related immune-mediated AEs were G1–2 (1 pt had 2 G3 infusion-related reactions). Conclusions: This risk-stratified, response-adapted approach offers a well-tolerated salvage strategy with high CMR rates and no new safety signals for CAYA with R/R cHL. Most pts avoided alkylator exposure prior to consolidation. Further follow up may confirm durability of disease control. Clinical trial information: NCT02927769. Research Sponsor: Bristol-Myers Squibb.

CMR and ORR per BICR and investigator (INV) in response-evaluable pts. BICR INV Any time before consolidation n 43 44 CMR, n (% [90% CI]) 38 (88 [77–95]) 39 (89 [78–95]) ORR, n (%) 42 (98) 43 (98) After 4 cycles nivolumab + BV induction n 44 44 CMR, n (%) 26 (59) 29 (66) ORR, n (% [90% CI]) 36 (82 [70–91]) 39 (89 [78–95])

8014 Poster Discussion Session; Displayed in Poster Session (Board #347), Fri, 8:00 AM-11:00 AM, Discussed in Poster Discussion Session, Fri, 8:00 AM-11:00 AM

Phase II, multicenter trial of nivolumab (Nivo) and brentuximab vedotin (BV) in patients (Pts) with untreated Hodgkin lymphoma (HL) over the age of 60 years or unable to receive standard ABVD chemotherapy: Results of a study of Academic and Community Cancer Research United (ACCRU) RU051505I.

Bruce D. Cheson, Nancy L. Bartlett, Betsy LaPlant, Hun Ju Lee, Ranjana H. Advani, Beth Christian, Catherine S. Magid Diefenbach, Tatyana Feldman, Stephen M. Ansell; Georgetown University Hospital, Washington, DC; Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO; Mayo Clinic, Rochester, MN; The University of Texas MD Anderson Cancer Center, Houston, TX; Stanford University, Stanford, CA; The Ohio State Univeristy, Columbus, OH; Perlmutter Cancer Center at NYU Langone Health, New York, NY; John Theurer Cancer Center, Hackensack, NJ

Background: HL is highly curable with . 90% of pts with limited and . 80% with advanced stage disease experiencing long-term disease-free survival. HL typically occurs in younger pts, yet 15-35% are . 60 yrs and experience a lower response rate, shorter survival, and greater toxicity. BV and checkpoint inhibitors have impressive activity in pts with relapsed and refractory HL. Thus, we initiated a phase II trial of BV-nivo in untreated pts with HL .60 yrs of age or considered unsuitable for standard ABVD therapy. Methods: Inclusion criteria: previously untreated pts with classical HL . 60 yrs or , 60 yrs but considered unsuitable for standard chemotherapy because of a cardiac ejection fraction of , 50%, diffusion capacity , 80%, or creatinine clearance . 30 but , 60 mL/min, or refused chemotherapy; ECOG PS 0-2, ANC .1500/mm3, platelets . 100,000/mm3, hemoglobin . 9 g/dl, bilirubin ,1.5 x upper limits of normal (ULN), aspartate/alanine transaminases , 2.5 x ULN, amylase and/or lipase , 1.5 x ULN, and serum creatinine , 2.0 mg/dl. Pts received BV at 1.8 mg/kg (cap at 180 mg) and nivo 3 mg/kg every 21 days for 8 cycles. Response was assessed per the Lugano Classification. Results: The study accrued 46 pts between May 13, 2016-January 30, 2019. Median age of 71.5 yrs, 69.5% had ECOG PS 1 or 2; 64% stage III or IV; 39.1% with B symptoms; 4.3% were , 60 years. Median follow-up was 21.2 months (range 2.9, 38.5), and 35 pts (76.1%) completed all 8 cycles of therapy. At the interim analysis (1st 25 pts) ORR was 64% (52% mCR, 12% pMR) which was lower than the projected 80%. In all 46 pts, 45.7% achieved mCR and 15.2% mPR (ORR 60.9%); in evaluable pts, best ORR was 95% with 68% mCR. No clinical factors predicted response. Neither median duration of response nor median survival has been reached. Median PFS is 21.8 months (17.8, Not reached). 22 pts experienced 33 treatment delays, primarily due to BV. 22 pts experienced peripheral neuropathy (5 grade 3). Grade 4 toxicities included increased transaminases (n = 1), increased lipase and/or amylase (n = 2), pancreatitis (1). One pt died from cardiac arrest, possibly treatment-related. Conclusions: BV-nivo is active in untreated older HL pts with comorbidities. How- ever, efficacy and response durability did not meet pre-specified criteria. Future trials based on these drugs, selecting pts most likely to benefit, may lead to a chemo-free approach for pts with HL. Clinical trial information: NCT02758717. Research Sponsor: Seattle Genetics, Bristol Myers Squibb.

8015 Poster Discussion Session; Displayed in Poster Session (Board #348), Fri, 8:00 AM-11:00 AM, Discussed in Poster Discussion Session, Fri, 8:00 AM-11:00 AM

Acalabrutinib (Acala) versus idelalisib plus rituximab (IdR) or bendamustine plus rituximab (BR) in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL): ASCEND final results.

Paolo Ghia, Andrzej Pluta, Malgorzata Wach, Daniel Lysak, Tomas Kozak, Martin Simkovic, Polina Kaplan, Iryna Kraychok, Arpad Illes, Javier De La Serna, Sean Dolan, Philip Campbell, Gerardo Musuraca, Abraham Jacob, Eric Joseph Avery, Jae Hoon Lee, Denise Wang, Priti Patel, Cheng Seok Quah, Wojciech Jurczak; Universita ` Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milan, Italy; Department of Hematological Oncology, Oncology Specialist Hospital, Brzozow, Poland; Department of Hemato-Oncology and Bone Marrow Transplantation, Medical University of Lublin, Lublin, Poland; Fakultnı´ Nemocnice Plzen, Pilsen, Czech Republic; Fakultnı´ Nemocnice Kralovske ´ Vinohrady, Prague, Czech Republic; University Hospital Hradec Kralove, Charles University, Hradec Kralove, Czech Republic; City Clinical Hospital No. 4 DCC, Dnipro, Ukraine; National Cancer Institute, Kiev, Ukraine; University of Debrecen, Faculty of Medicine, Department of Hematology, Debrecen, Hungary; Hospital Universitario 12 de Octubre, Madrid, Spain; Saint John Regional Hospital, University of New Brunswick, Saint John, NB, Canada; Barwon Health, University Hospital Geelong, Geelong, VIC, Australia; Istituto Scientifico Romag- nolo per lo Studio e la cura dei Tumori, Meldola, Italy; The Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, United Kingdom; Nebraska Hematology Oncology, Lincoln, NE; Gachon University Gil Medical Center, Incheon, South Korea; Acerta Pharma, South San Francisco, CA; Maria Sklodowska-Curie National Institute of Oncology, Krakow, Poland

Background: Acala is a next-generation, highly selective, covalent Bruton tyrosine kinase inhibitor approved for patients (pts) with CLL including those with R/R CLL. The efficacy and safety of acala alone vs IdR or BR were shown in R/R CLL pts in a preplanned interim analysis of ASCEND; final results are reported herein. Methods: In this randomized, multicenter, phase 3, open-label study (NCT02970318), R/R CLL pts were randomized 1:1 to receive oral (PO) acala 100 mg BID or investigator’s (INV) choice of IdR (Id: 150 mg PO BID until progression or toxicity; R: 375 x1 then 500 mg/m2 intravenously [IV] for 8 total infusions) or BR (B: 70 mg/m2 IV and R: 375 x1 then 500 mg/m2 IV for 6 total cycles) until progression or toxicity. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and safety were assessed. Results: 310 pts (acala, n=155; IdR, n=119; BR, n=36) were enrolled (median age: 67 y; del(17p) 16%, del(11q) 27%, Rai stage 3/4 42%). At a median follow-up of 22.0 m, acala significantly prolonged INV-assessed PFS vs IdR/BR (median: not reached vs 16.8 m; hazard ratio: 0.27, P,0.0001); 18-m PFS rates were 82% for acala and 48% for IdR/BR. 18-m OS rate was 88% for both treatment regimens. ORR was 80% with acala vs 84% with IdR/BR (ORR + partial response with lymphocytosis: 92% vs 88%, respectively). Common adverse events (AEs) are listed in the Table. AEs led to drug discontinuation in 16% of acala, 56% of IdR, and 17% of BR pts. AEs of interest included atrial fibrillation (acala 6%, IdR/BR 3%), major hemorrhage (all grade; acala 3%, IdR/ BR 3%), grade $3 infections (acala 20%, IdR/BR 25%), and second primary malignancies excluding non-melanoma skin cancer (acala 5%, IdR/BR 2%). Conclusions: Final ASCEND results with additional follow-up confirm earlier findings and support the favorable efficacy and safety of acala compared with standard-of-care regimens in R/R CLL pts. Clinical trial information: NCT02970318. Research Sponsor: Acerta Pharma, a member of the AstraZeneca group.

Acala IdR BR Any Any Any Grade Grade ‡3 Grade Grade ‡3 Grade Grade ‡3 Common AEsa, n (%) Headache 34 (22) 1 (1) 7 (6) 0 0 0 Neutropenia 33 (21) 26 (17) 54 (46) 47 (40) 12 (34) 11 (31) Diarrhea 30 (20) 3 (2) 58 (49) 29 (25) 5 (14) 0 Upper respiratory tract 30 (20) 3 (2) 19 (16) 4 (3) 4 (11) 1 (3) infection Cough 25 (16) 0 18 (15) 1 (1) 2 (6) 0 Anemia 24 (16) 19 (12) 11 (9) 8 (7) 4 (11) 3 (9) Pyrexia 21 (14) 1 (1) 22 (19) 8 (7) 6 (17) 1 (3) Fatigue 17 (11) 2 (1) 10 (9) 1 (1) 8 (23) 1 (3) Nausea 11 (7) 0 16 (14) 1 (1) 7 (20) 0 Infusion-related reaction 0 0 9 (8) 2 (2) 8 (23) 1 (3) aAny grade in $15% of pts

8016 Poster Discussion Session; Displayed in Poster Session (Board #349), Fri, 8:00 AM-11:00 AM, Discussed in Poster Discussion Session, Fri, 8:00 AM-11:00 AM

Tolerability and durable respones of the PI3Kd inhibitor ME-401 administered on an intermittent schedule in relapsed/refractory (R/R) follicular lymphoma (FL) and other B-cell malignancies.

Andrew David Zelenetz, Nishitha Reddy, Deepa Jagadeesh, Anastasios Stathis, Huda S. Salman, Jacob D. Soumerai, Vaishalee Padgaonkar Kenkre, Adam Steven Asch, Judith Llorin-Sangalang, Joanne Li, Igor Gorbatchevsky, John M. Pagel; Memorial Sloan Kettering Cancer Center, New York, NY; Vanderbilt University Medical Center, Nashville, TN; Cleveland Clinic Taussig Cancer Institute and Case Comprehensive Cancer Center, Cleveland, OH; IOSI-Oncology Institute of Southern Switzerland, Bellinzona, Switzerland; Stony Brook Medical Center, Stony Brook, NY; Massachusetts General Hospital, Boston, MA; University of Wisconsin, Madison, WI; University of Oklahoma Health Sciences Center, Oklahoma City, OK; MEI Pharma, Inc, San Diego, CA; Swedish Cancer Institute, Seattle, WA

Background: ME-401, a potent, selective, and structurally differentiated oral PI3kd inhibitor was evaluated in a dose escalation/expansion Phase 1b study, and previously demonstrated a high objective response rate (ORR) in FL and chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) when given on a continuous (CS) or an intermittent schedule (IS). IS appeared to significantly reduce the incidence of immune-mediated adverse events of special interest (AESI) associated with PI3kd inhibitors (diarrhea, rash, transaminase elevation, pneumonitis). We report maturing data from patients treated on the IS in this study. Methods: Eligible patients (pts) had FL, CLL/SLL, marginal zone lymphoma (MZL) and diffuse large B-cell lymphoma (DLBCL), at least 1 prior therapy, adequate bone marrow and organs function, ECOG status #2, and no prior PI3K therapy. IS dosing: ME-401 at 60 mg/day for two 28-day cycles, followed by 7 days of therapy every 28-day cycle until disease progression or intolerance. Pts received ME-401 monotherapy (n = 21) or a combination with rituximab (n = 36) given at 375 mg/m2 for 8 doses in Cycles 1-6. Results: Total of 57 pts treated with IS: 35 FL, 10 CLL/ SLL, 4 MZL, and 8 DLBCL with 38 (67%) currently still ongoing. Median age: 66 years (range 38-94) and median prior therapies: 2 (range 1-8). As of January 2020, median follow-up = 9.7 mo (range 0.6- 25.4+). Grade 3 AESI reported in 7 pts: 2 diarrhea (3.5%), 2 colitis (3.5%), 1 rash (2%), 1 ALT increased (2%), and 1 pneumonitis (2%). No Grade 3 AESI reported beyond Cycle 3. Discontinuation for AE in 3 pts (5%). There were no discernable safety differences between the monotherapy and rituximab combination groups. ORR was 83% in FL (76% in monotherapy group, 88% in combination group) and 89 % in CLL/SLL (100%, 83%), with median duration of response not reached. Median PFS was not reached in all patients with FL and CLL (combined analysis of both single agent and with rituximab). ORR was 100% (4/4) in MZL and 25 % (2/8) in DLBCL (in combination group only). Conclusions: ME-401 administered on an IS was well-tolerated, with a low-rate of Grade 3 class-related AESI and achieved a high-rate of durable objective responses in R/R indolent B-cell malignancies. These results may differentiate ME-401 and support further evaluation as a single-agent and in combination regimens. An ongoing global trial is evaluating ME-401 by IS in pts with FL after failure of $2 prior therapies (NCT03768505). Clinical trial information: NCT02914938. Research Sponsor: MEI Pharma, Inc.

8017 Poster Discussion Session; Displayed in Poster Session (Board #350), Fri, 8:00 AM-11:00 AM, Discussed in Poster Discussion Session, Fri, 8:00 AM-11:00 AM

Results of a completed phase I study of LAM-002 (apilimod dimesylate), a first-in-class phosphatidylinositol-3-phosphate 5 kinase (PIKfyve) inhibitor, administered as monotherapy or with rituximab or atezolizumab to patients with previously treated follicular lymphoma or other B-cell cancers.

Catherine S. Magid Diefenbach, Jonathan B Cohen, Wael A. Harb, Stephen M. Ansell, Loretta J. Nastoupil, Jeremy S. Abramson, Nehal J. Lakhani, Marshall T. Schreeder, Taimur Sher, Dipti Patel-Donnelly, David Michael Aboulafia, Candace A. Fuchs, Darrell Nix, Sean Landrette, Patricia S Graham, Lydia B King, Peter L. Young, Langdon L. Miller, Henri Lichenstein, Sarah C. Rutherford; Perlmutter Cancer Center at NYU Langone Health, New York, NY; Winship Cancer Institute, Emory University, Atlanta, GA; Horizon Oncology Research, LLC, Lafayette, IN; Mayo Clinic, Rochester, MN; The University of Texas MD Anderson Cancer Center, Department of Lymphoma/ Myeloma, Houston, TX; Massachusetts General Hospital Cancer Center; Harvard Medical School, Boston, MA; START-Midwest, Grand Rapids, MI; Clearview Cancer Institute, Huntsville, AL; Mayo Clinic, Jacksonville, FL; FNVHO, Fairfax, VA; Virginia Mason Medical Center, Seattle, WA; AI Ther- apeutics, Inc., Guilford, CT; Ce3, Inc, Guilford, CT; Weill Cornell Medicine, New York, NY

Background: LAM-002 is a selective inhibitor of PIKfyve that disrupts lysosomal homeostasis, inducing cytotoxicity in B-cell lymphoma models as monotherapy or with anti-CD20 or anti-PDL1 antibodies (Gayle et al., Blood 2017;129(13):1768). Methods: In this study, patients received LAM-002 orally 2-3 times per day (BID or TID) in a 3+3 escalation. Additional patients received LAM-002 125 mg BID as monotherapy; with rituximab 375 mg/m2 intravenously (IV) and or subcutaneously weekly (Q1W) x 4 → Q8W x 4; or atezolizumab 1200 mg IV Q3W until disease progression or unacceptable toxicity. Pharmacokinetics (PK) were assessed for 8 hours postdose on Days 1 and 8. Efficacy was evaluated Q6- 12W. Results: The study enrolled 62 patients (M:F n = 32/30); median [range] age = 69 [46-89] years; with diagnoses (n) of diffuse large B-cell lymphoma (25), follicular lymphoma (19), marginal zone lymphoma (8), mantle cell lymphoma (5), or chronic lymphocytic leukemia (5) to receive LAM-002 alone (n) at 50 mg BID (3), 100 mg BID (8), 150 mg BID (8), 75 mg TID (4), or 125 mg BID (20); LAM- 002/rituximab (12); or LAM-002/atezolizumab (7). During LAM-002 dose-ranging (50 mg BID → 100 mg BID → 150 mg BID → 75 mg TID → 125 mg BID) transient, reversible nausea and/or diarrhea occurred at 150 mg BID and 75 mg TID, resulting in a LAM-002 recommended Phase 2 dosing regimen (RP2DR) of 125 mg BID. Among 39 patients receiving LAM-002, 125 mg BID, alone or in combination for up to 22 cycles (1.9 years), adverse events were typically low-grade. LAM-002 PK showed rapid absorption, dose proportionality, minimal accumulation, and no substantive changes with rituximab or atezolizumab coadministration. In patients with follicular lymphoma and median [range] prior therapies = 3 [1-9] treated with the RP2DR, objective response rates were 2/7 (29%; 1 complete response [CR], 1 partial response [PR]) with LAM-002, 5/8 (63%; 1 CR, 4 PRs) with LAM-002/rituximab, and 2/2 (100%; 2 PRs) with LAM-002/atezolizumab. Conclusions: LAM-002, the first clinical PIKfyve inhibitor, is safe alone or with full-dose anti-CD20 or anti-PD-L1 inhibition. LAM-002 does not cause the myelosuppressive or immune adverse events associated with lenalidomide or PI3K inhibitors. Promising efficacy supports registration-directed Phase 2/3 testing of LAM-002 monotherapy and combination therapy for patients with previously treated follicular lymphoma. Clinical trial information: NCT02594384. Research Sponsor: AI Therapeutics, Inc.

8018 Poster Discussion Session; Displayed in Poster Session (Board #351), Fri, 8:00 AM-11:00 AM, Discussed in Poster Discussion Session, Fri, 8:00 AM-11:00 AM

Outcomes of GDPT (gemcitabine, cisplatin, prednisone,thalidomide) versus CHOP in newly diagnosed peripheral T-cell lymphoma patients.

Ling Li, Yuanyuan Sun, Xin Li, Lei Zhang, Xinhua Wang, Xiaorui Fu, Zhenchang Sun, Xudong Zhang, Zhaoming Li, Jingjing Wu, Hui Yu, Yu Chang, Jiaqin Yan, Xiaolong Wu, Zhiyuan Zhou, Feifei Nan, Tongyu Lin, Mingzhi Zhang, Tian Li; The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Zhengzhou University First Affiliated Hospital, Zhengzhou, China; Cancer Center Sun Yat-sen University, Guangzhou, China

Background: Peripheral T-cell lymphoma(PTCL) is highly heterogeneous invasive NHL.There is no consensus standard treatment for it now. So outcomes of GDPT versus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in treating newly diagnosed PTCL were compared. Methods: An open-label prospective clinical trial with 153 newly diagnosed PTCL patients conducted between January 2010 and December 2018 was designed. Patients were randomly assigned to the GDPT group (77 cases) and CHOP group (76 cases). Patients in each group were further divided into four subgroups: PTCL-NOS, ALCL, AITL, and an other types, in accordance with pathological patterns. Based on expression of RRM1, TOP2A, TUBB3 and ERCC1, patients were divided into groups with high and low gene expression levels. Clinical characteristics, side effects, efficacy, PFS and OS were compared. Results: There were no significant differences in the basic clinical features or side effects between the GDPT and CHOP groups. The ORR of the GDPT group was better than that of the CHOP group (66.3%vs. 50.0%, P= 0.042), as was the CR rate (42.9% vs. 27.6%, P= 0.049). Patients in the GDPT group had a longer PFS and OS than the CHOP group. The 4-year PFS and OS rates in the GDPT group were both superior to those in the CHOP group (63.6% vs. 53.0% for PFS, P= 0.035; 66.8% vs. 53.6% for OS, P= 0.039).In the GDPT group, the difference in CR between the four subgroups was statistically significant (P = 0.046).In the CHOP group, differences in both CR and ORR among the four subgroups were statistically significant (P= , 0.001 and P= 0.005, respectively).There were also statistically significant differences in CR between patients treated with CHOP and GDPT in the PTCL-NOS subgroup, AITL subgroup, and the other types subgroup(P= 0.015;P= 0.003;P= 0.005, respectively).The data also showed a significant difference in OS among the four subgroups within the GDPT group (P= 0.001).The OS of AITL was shorter than that of the other three subgroups. Four subgroups of CHOP showed a significant difference in PFS (P= 0.019). There was no statistical association between responses and the gene expression levels of RRM1, ERCC1, TUBB3 and TOP2A. Conclusions: The GDPT group had better response rates and prolonged the patients’ PFS and OS. As a promising new regimen, GDPT is expected to become the first-line therapy for PTCL. New agents should be applied to patients who do not achieve good responses with previous treatment, such as those diagnosed with angioimmunoblastic T cell lymphoma. Clinical trial information: NCT01664975. Research Sponsor: the National Natural Science Foundation of China, Provincial Medical Science and Technology Research Project in Henan.

8019 Poster Discussion Session; Displayed in Poster Session (Board #352), Fri, 8:00 AM-11:00 AM, Discussed in Poster Discussion Session, Fri, 8:00 AM-11:00 AM

Lenalidomide plus R-GDP (R2-GDP) in relapsed/refractory diffuse large B-cell lymphoma: Final results of the R2-GDP-GOTEL trial.

Luis de la Cruz Merino, Alejandro Martin, Esteban Nogales Fernandez, ´ Fernando Carnicero Gonzalez, ´ Eduardo Rıós Herranz, Fatima ´ de la Cruz-Vicente, Guillermo Rodriguez, Concepcion ´ Nicolas, ´ Natividad Martinez-Banaclocha, Josep Guma, Jose Gomez-Codina, ´ Antonio Salar Silvestre, Delvys Rodriguez- Abreu, Christina Quero Blanco, Jorge Labrador Gomez, ´ Maria Guirado, Natalia Palazon-Carri ´ on, ´ Pablo Espejo Garcıá, Mariano Provencio-Pulla, Antonio Rueda Dominguez; Clinical Oncology Depart- ment, Hospital Universitario Virgen Macarena, Seville, Spain; Hematology Department, Hospital Uni- versitario de Salamanca and IBSAL, CIBERONC, Salamanca, Spain; Hospital San Pedro de Alcántara, Cáceres, Spain; Hospital Universitario de Valme, Seville, Spain; Hematology Department, Virgen del Rocıó University Hospital, Seville, Spain; Hematology Department, Hospital Universitario Virgen del Rocıó, Seville, Spain; Hematology Department, Hospital Universitario Central de Asturias, Oviedo, Spain; General University Hospital de Elche, Elche, Spain; Hospital Universitari Sant Joan de Reus, IISPV, Universitat Rovira i Virgili, Reus, Spain; Hospital La Fe, Valencia, Spain; Hematology Department, Hospital del Mar, Barcelona, Spain; Hospital Universitario Insular de Gran Canaria, Las Palmas De Gran Canaria, Spain; Hospital Virgen de La Victoria, Málaga, Spain; Hospital Universitario de Burgos, Burgos, Spain; Clinical Oncology Department, Hospital General de Elche, Elche, Alicante, Spain; Clinical Oncology Department, Virgen Macarena University Hospital, Seville, Spain; Instituto Investigacion Sanitaria Puerta de Hierro-Segovia de Arana, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid,Spain;UGCOncologıá Intercentros, Hospitales Universitarios Regional y Virgen de la Victoria de Málaga, Instituto de Investigaciones Biomédicas de Málaga (IBIMA), Málaga, Spain

Background: Lenalidomide is an immunomodulatory drug that could reverse rituximab refractoriness in lymphoma patients (pts). We conducted an open label multicenter phase 2 trial testing the efficacy and toxicity of a combination of lenalidomide and rituximab (R2) plus GDP schedule (R2-GDP) in Relapsed/ Refractory Diffuse Large B Cell Lymphoma (R/R DLBCL) pts, not suitable for autologous stem cell transplant (ASCT). Methods: Patients with R/R DLBCL previously treated with at least 1 prior line of immunochemotherapy including rituximab, and not candidates for ASCT, were eligible. After a run-in phase period, treatment consisted of an induction phase with lenalidomide (LEN) 10 mg po d1-14, rituximab 375 mg/m2 iv d1, cisplatin 60 mg/m2 iv d1, gemcitabine 750 mg/m2 iv d1 and d8 and dexamethasone 20 mg d1-3, up to a maximum of 6 cycles. Pts without disease progression (DP) entered into a maintenance phase with LEN 10 mg, or last LEN dose received in the induction phase, d1-21 in cycles every 28 days. Primary endpoint was overall response rate (ORR) by investigator assessment. Secondary endpoints included disease free survival (DFS), event free survival (EFS), overall survival (OS), safety and response by cell of origin (COO), type of DLBCL (double-triple hit) and other microenvironment and genomic biomarkers. Results: 79 pts were enrolled between April 2015 and September 2018. Median age was 70 years (range 23-86), 48,7% women. 78 pts were considered for efficacy and safety in the intention to treat (ITT) analysis. With a median follow-up of 13 months at the time of cut-off (November 2019), ORRwas 59.0%, with 32.1% complete responses (CR) and 26.9% partial responses (PR). In the primary refractory population (n = 33), ORR was 45.5%, with 21.2% CR and 24.3% PR. There were no statistically significant differences in ORR with respect to COO. In Double-Hit R/R DLBCL (n = 16), ORR was 37.5% with 25% CR. Median OS was 12.0 months (6.9-17.0). Most common grade 3/4 (G3/4) adverse events were thrombocytopenia (60.2%), neutropenia (60.2%) and anemia (26.9%). Febrile neutropenia occurred in 14.1% pts. Most frequent non- hematologic G3/4 events were asthenia (19.2%), infection (15.3%) and renal insufficiency (6.4%). There were 4 toxic deaths related to the R2-GDP schedule. Conclusions: LEN with Rituximab and GDP (R2-GDP) is feasible and active in R/R DLBCL. Results in the primary refractory DLBCL population are particularly promising. Analysis of COO did not revealed differences in response rates. Immune biomarkers results will be showed at the meeting. Clinical trial information: EudraCT 2014- 001620-29. Research Sponsor: CELGENE.

8020 Poster Discussion Session; Displayed in Poster Session (Board #353), Fri, 8:00 AM-11:00 AM, Discussed in Poster Discussion Session, Fri, 8:00 AM-11:00 AM

RE-MIND study: A propensity score-based 1:1 matched comparison of tafasitamab + lenalidomide (L-MIND) versus lenalidomide monotherapy (real-world data) in transplant- ineligible patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

Grzegorz S. Nowakowski, Thomas David Rodgers, Dario Marino, Maurizio Frezzato, Anna Maria Barbui, Claudia Castellino, Erika Meli, Nathan Hale Fowler, Bruce A. Feinberg, Sascha Tillmanns, Stephan Parche, Guenter Fingerle-Rowson, Mark Winderlich, Sumeet Vijay Ambarkhane, Gilles A. Salles, Pier Luigi Zinzani; Division of Hematology, Mayo Clinic, Rochester, MN; University of Rochester Medical Center, Rochester, NY; Medical Oncology 1, Department of Oncology, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy; Azienda ULSS 8 Berica, Vicenza, Italy; ASST Papa Giovanni XXIII, Bergamo, Italy; Hematology Division, Santa Croce and Carle Hospital, Cuneo, Italy; ASST Grande Ospedale Metropolitano Niguarda, Dipartimento di Ematologia e Oncologia, S.C. Ematologia, Milan, Italy; Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX; Cardinal Health Inc., Dublin, OH; MorphoSys AG, Planegg, Germany; H´ematologie, Hospices Civils de Lyon and Universite ´ de Lyon, Lyon, France; Institute of Hematology L e A Seragnoli, ` University of Bologna, Bologna, Italy

Background: Patients with R/R DLBCL ineligible for autologous stem cell transplant (ASCT) have a poor prognosis. In these patients, tafasitamab (anti-CD19 antibody) plus lenalidomide (LEN) has shown encouraging results in the open-label, single-arm, phase II L-MIND study (n = 81; NCT02399085). To evaluate the contribution of tafasitamab to the activity of this doublet, we conducted a global, real- world study of patients treated with LEN monotherapy (RE-MIND; NCT04150328). Here we present the primary analysis of a 1:1 patient-level matched comparison between the L-MIND and RE-MIND cohorts. Methods: Patients treated with LEN monotherapy for R/R DLBCL were enrolled in the observational, retrospective RE-MIND cohort. As in L-MIND, patients had 1–3 prior systemic therapies, including $1 CD20-targeting regimen; were aged $18 years; and were not eligible for ASCT. A 1:1 estimated propensity score (ePS) matching methodology ensured balancing of nine pre-specified baseline covariates. The primary analysis set, Matched Analysis Set 25 (MAS25), included patients who received a LEN starting dose of 25 mg/day. The primary endpoint was investigator-assessed best objective response rate (ORR). Key secondary endpoints included overall survival (OS) and complete response (CR) rate. Results: 490 patients were enrolled in RE-MIND across 58 centers in the US and Europe, of which 140 fulfilled the ePS matching criteria. The MAS25 included 76 patients each from the two cohorts. Baseline characteristics between cohorts were comparable. The primary endpoint was met with a significantly better ORR of 67.1% (95% CI: 55.4–77.5) for the L-MIND cohort versus 34.2% (95% CI: 23.7–46.0) for the RE-MIND cohort (odds ratio 3.89; 95% CI: 1.90–8.14; p , 0.0001). The CR rate was 39.5% (95% CI: 28.4–51.4) in the L-MIND cohort and 13.2% (95% CI: 6.5–22.9) in the RE-MIND cohort. A significant difference in OS favored the L-MIND cohort (HR = 0.499; 95% CI: 0.317–0.785). ORR and CR outcomes in the RE-MIND cohort were similar to the published literature for LEN monotherapy in R/R DLBCL. Conclusions: Significantly better ORR, CR and OS indicate potential synergistic effects of the tafasitamab + LEN combination in ASCT-ineligible R/R DLBCL. ePS-based 1:1 matching allows robust estimation of the treatment effect of tafasitamab when added to LEN. RE-MIND demonstrates the utility of real-world data in interpreting non-randomized trials. Clinical trial information: NCT04150328. Research Sponsor: MorphoSys AG.

8021 Poster Session (Board #354), Fri, 8:00 AM-11:00 AM

Autologous stem cell transplantation for untreated transformed indolent B-cell lymphoma in first remission: An international, multicenter propensity matched study.

Collin K Chin, Kenneth JC Lim, Katharine L Lewis, Preetesh Jain, Yun Qing, Lei Feng, Chan Cheah, John Francis Seymour, David Ritchie, Kate Burbury, Constantine Si Lun Tam, Nathan Hale Fowler, Luis Fayad, Jason Westin, Sattva Swarup Neelapu, Fredrick B. Hagemeister, Felipe Samaniego, Christopher Flowers, Loretta J. Nastoupil, Michael Dickinson; The University of Texas MD Anderson Cancer Center, Department of Lymphoma/Myeloma, Houston, TX; Peter MacCallum Cancer Centre & Royal Melbourne Hospital, Melbourne, Australia; Sir Charles Gairdner Hospital, Nedlands, Australia; The University of Texas MD Anderson Cancer Center, Department of Biostatistics, Houston, TX; Peter MacCallum Cancer Centre, Melbourne, University of Melbourne, Parkville, Victoria, Australia; Peter MacCallum Cancer Centre & University of Melbourne, Melbourne, Australia

Background: Transformation of untreated indolent B-cell lymphoma (Tr-iNHL) is associated with poor outcomes. Current practices are extrapolated from prospective studies of de novo large B-cell lymphoma (DLBCL) or small retrospective studies. High dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) is used as consolidation in first remission (CR1) in some centers but the evidence-base is weak. Methods: CLL/SLL, MCL as primary diseases and non-DLBCL transformations were excluded. Propensity score analysis (PSM) using the “greedy match” algorithm was used to match the baseline covariates to adjust for potential selection bias. Landmark analysis was performed with time zero at 3 months after completion of front line chemotherapy (FLC). Kaplan-Meier method and the Cox proportional hazards model were was used for time-to-event analysis including progression-free survival (PFS) and overall survival (OS). Results: 319 transplant eligible patients (age ,75, LVEF .45%, no severe lung disease, CR by PET or CT .3 months after FLC) who received ./= standard RCHOP intensity FLC were identified across three centers in Australia & US. 283 (89%) patients had follicular lymphoma, 30 (9%) marginal zone lymphoma, 6 (2%) other subtypes. 49 patients underwent HDC and ASCT in CR1, a matched cohort of 98 pts based on age, stage, HGBL-DH and ECOG PS at diagnosis was generated with a 1:2 ratio using PSM. After a median follow-up of 3.6 (min: 0.1, max: 18.3) years, ASCT was associated with significantly superior PFS on multivariable analysis (MVA) (HR 0.51, 0.27-0.98; P=0.043). Univariate analysis demonstrated a trend towards inferior OS in the ASCT cohort (HR 2.36; 0.87-6.42; P=0.092) with more deaths in the ASCT arm due to PD (8% v 4%). Of the 40 patients (41%) with relapsed disease in the non-ASCT cohort–15 patients underwent salvage HDC & ASCT with 7/15 (47%) ongoing CR; 10 patients underwent CAR-T therapy (5 relapse post ASCT, 4 refractory disease, 1 relapse post FLC) with 6/10 (60%) ongoing CR; 3 patients underwent allogeneic SCT (2 relapse post ASCT, 1 relapse post FLC) with 2/3 (67%) ongoing CR. Conclusions: Although ASCT in CR1 may improve initial duration of disease control in de novo Tr-iNHL, the impact on OS is less clear with effective salvage therapies in the CAR-T era. Research Sponsor: None.

8022 Poster Session (Board #355), Fri, 8:00 AM-11:00 AM

Effect of adding ublituximab to ibrutinib on PFS, ORR, and MRD negativity in previously treated high-risk chronic lymphocytic leukemia: Final results of the GENUINE phase III study.

Jeff P. Sharman, Danielle M. Brander, Anthony R. Mato, Nilanjan Ghosh, Stephen J. Schuster, Suman Kambhampati, John M. Burke, Frederick Lansigan, Marshall T. Schreeder, Scott D Lunin, Alexander Zweibach, Mikhail Shtivelband, Patrick M. Travis, Jason Claud Chandler, Kathryn S. Kolibaba, Peter Sportelli, Hari P. Miskin, Michael S. Weiss, Ian Flinn; Willamette Valley Cancer Institute and US Oncology Research Center, Eugene, OR; Duke University School of Medicine, Durham, NC; Center for CLL, Memorial Sloan Kettering Cancer Center, New York, NY; Levine Cancer Institute, Atrium Health, Charlotte, NC; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA; University of Kansas Medical Center, Sarah Cannon Research Institute, Kansas City, KS; Rocky Mountain Cancer Centers/US Oncology Research, Aurora, CO; Dartmouth-Hitchcock Medical Center, Lebanon, NH; Clearview Cancer Institute, Huntsville, AL; Florida Cancer Specialists, Sarah Cannon Research Institute, Sarasota, FL; Cancer Care Centers of South Texas/US Oncology Research, New Braunfels, TX; Ironwood Cancer and Research Centers, Chandler, AZ; Highlands Oncology Group, Fayetteville, AR; West Cancer Center, Memphis, TN; Compass Oncology, US Oncology Research, Vancouver, WA; TG Therapeutics, Inc., New York, NY; Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN

Background: The BTK inhibitor ibrutinib (IB) has advanced the treatment for patients (pts) with CLL, however, among pts with high-risk CLL, disease control with IB is less durable. Ublituximab (UTX) is a glycoengineered mAb with enhanced ADCC. The GENUINE study evaluated the addition of UTX to IB vs. IB alone in high-risk rel/ref CLL. With a median follow up now 3.5+ yrs, we present the final results. Methods: Eligible pts having rel/ref CLL with centrally confirmed del17p, del11q, and/or a TP53 mutation, were randomized 1:1 to IB (420 mg QD) alone or with UTX (900 mg on D1, 8, 15 of Cy 1, D1 of Cy 2-6, and Q3 Cy thereafter). No limit on # of prior Tx; prior IB excluded. Primary endpoint was overall response rate (ORR) by iwCLL 2008 (excludes PR-L); secondary endpoints were CR rate, peripheral blood MRD negativity (analyzed centrally), PFS, and safety. Response was by blinded independent review. Results: 117 pts were treated (59 in UTX + IB arm; 58 in IB arm). Med age was 66 yrs and med # of prior Tx was 1 (range 1-5) for each arm. Baseline features were relatively balanced including ECOG, gender, and med time since diagnosis (6+ yrs). 17p del was greater in the IB arm (50% vs 44%); bulky disease was greater in UTX + IB arm (47% vs 28%); IGHV-unmut was 83% for both arms. At data-cutoff of Sep 1, 2019, AEs were comparable between the arms, except infusion reactions (UTX + IB: All G 53% / G 3/4 3%) and neutropenia (All G 36% vs 21%, G 3/4 19% vs. 12%) which were higher for UTX + IB. At a med follow up of 42 mos, all efficacy endpoints were in favor of UTX + IB (see Table). Conclusions: In contrast to prior studies adding rituximab to IB, GENUINE is the first randomized trial to demonstrate a PFS benefit with the addition of an anti-CD20 to IB. Increasing depth of response (CR rate, MRD-neg) post first year of Tx supports maintenance therapy with UTX. Clinical trial information: NCT02301156. Research Sponsor: TG Therapeutics, Inc.

Efficacy UTX + IB Ibrutinib p-value ORR (CR/CRi, PR) 53 (90%) 40 (69%) p , 0.01 CR/CRi 12 (20%) 3 (5%) p , 0.05 ORR (CR/CRi, PR, PR-L) 55 (93%) 45 (77.5%) p , 0.05 MRD-neg 27 (46%) 4 (7%) p , 0.0001 PFS (All pts; N = 117) Med NR (NE, NE) Med 35.9 mos (17, NE) p = 0.016 HR 0.455 (95%CI: 0.239 0.865) PFS (17p del and/or p53; Med NR (NE, NE) Med 18.9 mos (11.4, NE) p = 0.004 N = 63) HR 0.253 (95%CI: 0.099 0.646) OS HR 0.532 (95%CI: 0.241 1.174) p = 0.118 PFS was superior for UTX + IB vs. IB alone, driven primarily by pts with del17p/p53mut. No meaningful difference in PFS was observed for pts with del11q. Among pts treated with UTX + IB, MRD-neg was associated with significant improvement in PFS. OS at 4 yrs was 82% vs. 70% for UTX + IB vs. IB alone.

8023 Poster Session (Board #356), Fri, 8:00 AM-11:00 AM

Comparison of efficacy and safety with obinutuzumab plus chemotherapy versus rituximab plus chemotherapy in patients with previously untreated follicular lymphoma: Updated results from the phase III Gallium Study.

William Townsend, Christian Buske, Guillaume Cartron, David Cunningham, Martin J.S. Dyer, John G. Gribben, Zilu Zhang, Kaspar Rufibach, Tina Nielsen, Michael Herold, Wolfgang Hiddemann, Robert Marcus; Cancer Research UK and UCL Cancer Trials Centre, London, United Kingdom; Uni- versit¨atsklinikum Ulm, Ulm, Germany; CHU de Montpellier, Montpellier, France; Royal Marsden Hospital, Sutton, United Kingdom; Ernest and Helen Scott Haematological Research Institute, University of Leicester, Leicester, United Kingdom; St Bartholomew’s Hospital, London, United Kingdom; F. Hoffmann-La Roche Ltd., Shanghai, China; F. Hoffmann-La Roche Ltd., Basel, Switzerland; HELIOS- Klinikum Erfurt, Erfurt, Germany; Department of Medicine III, Ludwig-Maximilians-University Hospital Munich, Munich, Germany; HCA Healthcare, London, United Kingdom

Background: Immunochemotherapy is standard of care for patients (pts) with previously untreated advanced stage follicular lymphoma (FL). Four-year data from the Phase III GALLIUM study (NCT01332968) have previously demonstrated an improvement in the primary endpoint of investigator-assessed progression-free survival (PFS) for obinutuzumab (GA101, G) plus chemotherapy (G-chemo) versus rituximab plus chemotherapy (R-chemo) (Townsend et al. ASH 2018). Here, we report efficacy and safety results from an updated analysis. Methods: Eligibility criteria: $18 years; advanced stage, previously untreated grade 1–3a FL; requiring treatment according to Groupe d’Etude des Lymphomes Folliculaires criteria. Pts were randomized 1:1 to receive G 1000mg IV (day [D] 1, 8 and 15 of Cycle 1; D1 of each subsequent cycle) or R 375mg/m2 IV (D1 of each cycle) with CHOP, CVP, or bendamustine for 6 or 8 cycles. Responders received maintenance therapy with the same monoclonal antibody every 2 months for 2 years. Results: 1202 pts (median age 59 years) were enrolled (n = 601 per treatment arm). Median duration of follow-up was 76.5 months. Pts receiving G- vs R-chemo demonstrated improved PFS (5-year PFS: hazard ratio [HR] 0.76; 95% CI: 0.62–0.92; p = 0.0043; 70.5% [95% CI: 66.4–74.1] vs 63.2% [95% CI: 59.0–67.1]). There was no notable difference in 5-year overall survival (OS), with few events in either arm (HR 0.87; 95% CI: 0.62–1.22; p = 0.41; G-chemo: 90.2% [95% CI: 87.5–92.4]; R-chemo: 89.4% [95% CI: 86.6–91.6]). Time-to-next- treatment (TTNT) was greater in the G- vs R-chemo arm (5-year TTNT rate: HR 0.72; 95% CI: 0.57–0.90; p = 0.0039; 79.7% [95% CI: 76.1–82.7] vs 72.9% [95% CI: 69.1–76.4]). Incidence of grade 3–5 adverse events was 79.3% in the G-chemo arm and 71.2% in the R-chemo arm, and consistent with those reported in the primary analysis (Marcus et al. N Engl J Med 2017). Conclusions: These data further demonstrate the clinically meaningful and durable benefit of treatment with G-chemo relative to R-chemo in previously untreated FL pts. Acknowledgement: GALLIUM was sponsored by F. Hoffmann-La Roche Ltd. Third-party medical writing assistance, under the direction of William Townsend, was provided by Louise Profit and Stephanie Lacey of Gardiner-Caldwell Communications, and was funded by F. Hoffmann-La Roche Ltd. Clinical trial information: NCT01332968. Research Sponsor: F. Hoffmann-La Roche Ltd.

8024 Poster Session (Board #357), Fri, 8:00 AM-11:00 AM

Acalabrutinib in treatment-na¨ıve chronic lymphocytic leukemia: Mature results from phase II study demonstrating durable remissions and long-term tolerability.

John C. Byrd, Jennifer Ann Woyach, Richard R. Furman, Peter Martin, Susan Mary O’Brien, Jennifer R. Brown, Deborah Marie Stephens, Jacqueline Claudia Barrientos, Stephen Devereux, Peter Hillmen, John M. Pagel, Ahmed M. Hamdy, Raquel Izumi, Priti Patel, Min Hui Wang, Nitin Jain, William G. Wierda; The Ohio State University Comprehensive Cancer Center, Columbus, OH; Weill Cornell Medicine, New York Presbyterian Hospital, New York, NY; Chao Family Compre- hensive Cancer Center, University of California, Irvine, CA; Dana-Farber Cancer Institute, Boston, MA; University of Utah Huntsman Cancer Institute, Salt Lake City, UT; Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY; College Hospital, NHS Foundation Trust Denmark Hill, London, United Kingdom; St. James’s University Hospital, Leeds, United Kingdom; Swedish Cancer Institute, Seattle, WA; Acerta Pharma, South San Francisco, CA; The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX

Background: The next-generation Bruton tyrosine kinase inhibitor acalabrutinib was approved in patients (pts) with treatment-na¨ıve (TN) and relapsed/refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) based on two complementary phase 3 studies, ELEVATE- TN and ASCEND. This report of ACE-CL-001 (NCT02029443), the first phase 2 study of acalabrutinib, provides the longest safety and efficacy follow-up to date in symptomatic TN CLL pts. Methods: Adults with TN CLL/SLL were eligible if they met iwCLL 2008 criteria for treatment, were inappropriate for/ declined standard chemotherapy and had ECOG performance status 0–2. Pts received acalabrutinib 100 mg BID or 200 mg QD, later switching to 100 mg BID, until progressive disease (PD) or unacceptable toxicity. Primary endpoint was safety. Events of clinical interest (ECI) were based on combined AE terms for infections, bleeding events, hypertension, and second primary malignancies (SPM) excluding non-melanoma skin, and on a single AE term for atrial fibrillation. Additional endpoints included investigator-assessed overall response rate (ORR), duration of response (DOR), time to response (TTR), and event-free survival (EFS). Results: Ninety-nine pts (n = 62 100 mg BID; n = 37 200 mg QD), were treated [median age: 64 years, 47% Rai stage 3–4 disease, 10% del(17p), 62% unmutated IGHV]. At median follow-up of 53 months (range, 1–59), 85 (86%) pts remain on treatment; most discontinuations were due to AEs (n = 6) or PD (n = 3 [n = 1 Richter transformation]). Most common AEs (any grade) were diarrhea (52%), headache (45%), upper respiratory tract infection (44%), arthralgia (42%), and contusion (42%). All-grade and grade $3 ECIs included infection (84%, 15%), bleeding events (66%, 3%), and hypertension (22%, 11%). Atrial fibrillation (all grades) occurred in 5% of pts (incidence: 1% in years 1, 2, 4; 3% in year 3). SPMs excluding non-melanoma skin (all grades) occurred in 11%. Serious AEs were reported in 38% of pts; those in . 2 pts were pneumonia (n = 4) and sepsis (n = 3). ORR was 97% (7% complete response; 90% partial response). Median TTR was 3.7 months (range, 2–22). Response rates were similar across high-risk groups. Median DOR and median EFS were not reached; 48-month DOR rate was 97% (95% CI, 90%–99%), and 48-month EFS rate was 90% (95% CI, 82%–94%). Conclusions: Long-term data from ACE-CL-001 further support the favorable results with acalabrutinib in phase 3 studies and demonstrate durable responses with no new long-term safety issues. Clinical trial information: NCT02029443. Research Sponsor: Acerta Pharma, a member of the AstraZeneca group.

8025 Poster Session (Board #358), Fri, 8:00 AM-11:00 AM

First-line immunochemotherapy for follicular lymphoma in the GALLIUM study: Prognostic value of PET-CT status after long-term follow-up.

Tina Nielsen, Sally Barrington, Michel Meignan, Deniz Sahin, Andrea Knapp, Anastasiia Kinkolykh, Michael Herold, Wolfgang Hiddemann, Robert Marcus, Judith Trotman; F. Hoffmann-La Roche Ltd., Basel, Switzerland; King’s College London and Guys’ & St Thomas PET Imaging Centre, School of Biomedical Engineering and Imaging Sciences, King’s College London, London, United Kingdom; Service de Medecine ´ Nucleaire, ´ Hopitalˆ Henri Mondor and Universite ´ Paris Est Creteil, ´ Creteil, ´ France; Consultant to F. Hoffmann-La Roche Ltd., via GCE Solutions-an IQVIA business, Basel, Switzerland; HELIOS-Klinikum Erfurt, Erfurt, Germany; Department of Medicine III, Ludwig-Maximilians-University Hospital Munich, Munich, Germany; HCA Healthcare, London, United Kingdom; Hematology Depart- ment, Concord Repatriation General Hospital, University of Sydney, Concord, Australia

Background: The prognostic value of 18F-fluorodeoxyglucose (FDG) positron emission tomography- computed tomography (PET-CT) response assessment following first-line immunochemotherapy for advanced-stage symptomatic follicular lymphoma (FL) was previously demonstrated for patients (pts) enrolled in the Phase III GALLIUM study (NCT01332968; Trotman et al. ICML 2017). Here, we evaluated the association between PET complete metabolic response (CMR) and survival after longer follow-up in this patient population. Methods: In the GALLIUM study, 1202 pts with previously untreated FL were randomized 1:1 to induction therapy of 1000mg obinutuzumab (G; Days 1, 8, 15 of Cycle 1 then Day 1 of subsequent cycles) or 375mg/m2 rituximab (R; Day 1 of each cycle), in combination with chemotherapy (CHOP, CVP, or bendamustine) (Marcus et al. New Engl J Med 2017). PET-CT scans were mandatory, where available, at baseline and end-of-induction (EOI) for the first 170 pts enrolled, and optional thereafter. For this response analysis, the Lugano 2014 criteria were applied by an independent review committee (IRC) (Cheson et al. J Clin Oncol 2014). Associations between EOI PET complete metabolic response (PET-CMR) status and progression-free survival (PFS) and overall survival (OS) were evaluated, with hazard ratios (HR) stratified according to chemotherapy regimen and FL International Prognostic Index. Results: Of the 609 pts with a baseline PET scan, 595 (98%) had detectable lesions. Of these, 519 pts had an EOI PET evaluable by Lugano 2014 criteria. At EOI, per IRC assessment, 450/595 (76%) pts had achieved CMR. Pts with non-available scans were considered as non-responders and were excluded from the landmark (LM) analyses. Pts who died or progressed (CT- based progression assessment) before or at EOI were excluded from the PFS LM analysis; pts who died before EOI were excluded from the OS LM analysis. After a median follow-up of 76.5 months, EOI PET status was highly prognostic for both longer investigator-assessed PFS (non-CMR vs CMR: HR 3.40; 95% CI: 2.33–4.97; p , 0.0001) and longer OS (HR 3.34; 95% CI: 1.81–6.17; p , 0.0001). Six-year investigator-assessed PFS from EOI was 62.6% (95% CI: 57.0–67.6) for CMR pts compared with 23.4% (95% CI: 12.2–36.7) for non-CMR pts; the corresponding OS was 91.3% (95% CI: 88.1–93.6) vs 79.6% (95% CI: 68.0–87.4). Conclusions: With more than 6 years of follow-up, this analysis confirms that after first-line chemoimmunotherapy for FL, achieving CMR on PET-CT is an early and strong predictor of increased PFS and OS. Clinical trial information: NCT01332968. Research Sponsor: GALLIUM was sponsored by F. Hoffmann-La Roche Ltd. Third-party medical writing assistance, under the direction of Judith Trotman, was provided by Aisling Lynch and Katie Smith of Gardiner-Caldwell Communications, and was funded by F. Hoffmann-La Roche Ltd.

8026 Poster Session (Board #359), Fri, 8:00 AM-11:00 AM

Cause of death in patients with newly diagnosed chronic lymphocytic leukemia (CLL) stratified by the CLL-International Prognostic Index (CLL-IPI).

Yucai Wang, Sara J Achenbach, Kari G. Rabe, Tait D. Shanafelt, Timothy Call, Wei Ding, Saad Kenderian, Eli Muchtar, Jose Francisco Leis, Amber Koehler, Susan M. Schwager, James Robert Cerhan, Susan L. Slager, Neil E. Kay, Sameer Ashok Parikh; Mayo Clinic, Rochester, MN; Stanford University Medical Center, Stanford, CA; Mayo Clinic, Scottsdale, AZ; Department of Health Sciences Research, Mayo Clinic, Rochester, MN

Background: CLL progression and CLL-related complications (infections and second malignancies) were the leading cause of death (COD) in a prospective cohort of CLL patients (Strati, BJH 2017). The CLL-IPI integrates major clinical and molecular prognostic factors and stratifies patients into 4 risk groups with distinct prognosis. It is unknown if COD differs according to CLL-IPI risk group in patients with newly diagnosed CLL. Methods: Patients diagnosed with CLL between 1/2000-12/2019 and seen within 1 year of diagnosis were identified from the Mayo Clinic CLL database. Cumulative incidences of cause-specific death were analyzed using Gray’s test, with deaths from different causes treated as competing events and deaths from unknown causes excluded. Results: 1276 patients were included in this study. The median age at diagnosis was 63 years (range 24-92), and 880 (69%) were male. Based on CLL-IPI score, 449 (35%) had low risk disease, 443 (35%) had intermediate risk disease, and 384 (30%) had high/very high risk disease. Median follow-up time for the study was 6 years; 286 deaths occurred. The COD was CLL progression in 99 (35%), infection in 16 (6%), second malignancy in 47 (16%), CLL-unrelated in 59 (21%), and unknown in 65 (23%) patients. The rates of death due to CLL progression were higher (17.3% at 5 years; 30.3% at 10 years) than the rates due to CLL-related complications (5.7% at 5 years; 12.9% at 10 years) or due to CLL-unrelated causes (8.6% at 5 years; 16.9% at 10 years) in the CLL-IPI high/very high risk group, but not the CLL-IPI low or intermediate risk group (Table). A higher CLL-IPI risk group was associated with a higher rate of death due to CLL progression (P , 0.001), as well as a higher rate of death due to CLL-related complications (P = 0.013), and CLL-unrelated causes (P , 0.001). Conclusions: Causes of death in newly diagnosed CLL patients differ according to their CLL-IPI risk group. In patients with high/very high risk CLL, improving CLL disease control with novel agents seems justified. In patients with low/intermediate risk CLL, there should be increased efforts to reverse immune dysfunction to reduce infections and second malignancies. Research Sponsor: None.

Cumulative Incidence of Death (%) CLL-related compli- CLL cations (infection or CLL- progression second malignancy) unrelated 5-yr 10- P 5-yr 10- P 5-yr 10- P yr value yr value yr value All patients 5.7 13.2 3.2 8.5 3.8 8.7 CLL-IPI risk , 0.013 , 0.001 0.001 Low 0.3 2.8 2.1 6.4 0.6 3.6 Intermediate 2.0 10.4 2.5 7.0 3.1 7.4 High/Very 17.3 30.3 5.7 12.9 8.6 16.9 high

8027 Poster Session (Board #360), Fri, 8:00 AM-11:00 AM

Fixed-duration venetoclax-obinutuzumab for previously untreated patients with chronic lymphocytic leukemia: Follow-up of efficacy and safety results from the multicenter, open- label, randomized, phase III CLL14 trial.

Othman Al-Sawaf, Can Zhang, Maneesh Tandon, Arijit Sinha, Anna Maria Fink, Sandra Robrecht, Eugen Tausch, William L. Schary, Matthias Ritgen, Clemens Martin Wendtner, Karl A Kreuzer, Barbara Eichhorst, Stephan Stilgenbauer, Michael J. Hallek, Kirsten Fischer, CLL14 Study Investi- gators; Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, German CLL Study Group, University of Cologne, Cologne, Germany; University Hospital of Cologne, Dep I of Internal Medicine, Cologne, Germany; Roche Products Ltd, Welwyn Garden City, United Kingdom; Roche Products Limited, Welwyn Garden City, Welwyn Garden City, United Kingdom; Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, University Hospital, Cologne, Germany; Ulm University, Ulm, Germany; Sunesis Pharmaceuticals Inc., South San Francisco, CA; Department of Internal Medicine II: Hematology and Oncology, University Medical Center Schleswig- Holstein, Campus Kiel, Kiel, Germany; Klinikum Schwabing, Department of Hematology, Oncology, Immunology, Palliative Care, Infectious Diseases and Tropical Medicine, Munich, Germany; University Hospital Cologne, Cologne, Germany; Department of Internal Medicine III, University of Ulm, Ulm, Germany; University of Cologne, Cologne, Germany

Background: The CLL14 trial demonstrated significant improvement of progression-free survival (PFS) with fixed-duration venetoclax-obinutuzumab (VenG) as compared to chlorambucil-obinutuzumab (ClbG) in patients with previously untreated CLL and coexisting conditions. Here, we report follow-up data on safety and efficacy. Methods: Patients with previously untreated CLL and coexisting conditions were randomized 1:1 to receive 12 cycles of venetoclax with 6 cycles of obinutuzumab or 12 cycles of chlorambucil with 6 cycles of obinutuzumab. Primary endpoint was investigator-assessed progression- free survival. Key secondary endpoints were response rates, rates of minimal residual disease (measured every 6 months up to 5 years after last patient enrolment) and overall survival. Follow-up is ongoing but all patients are off study treatment. This trial was registered with ClinicalTrials.gov, number NCT02242942. Results: Of the 432 enrolled patients, 216 were randomly assigned to receive VenG and 216 to receive ClbG. After a median follow-up of 39.6 months (interquartile range 36.75 - 43.04), progression-free survival continued to be superior for VenG as compared to ClbG (median not reached vs 35.6 months; hazard ratio [HR] 0.31 [0.22-0.44], p , 0.001). At 3 years, the estimated progression- free survival rate was 81.9% in the VenG arm and 49.5% in the ClbG arm. This benefit was consistently observed across all clinical and biological risk groups, including patients with TP53 mutation/deletion and unmutated IGHV status. Of note, PFS was also significantly longer for VenG treated patients with mutated IGHV status. Assessment of minimal residual disease 18 months after end of treatment showed that 47.2% of patients in the VenG arm had undetectable (u) uMRD ( , 1024), 13% had low (L)-MRD ($ 1024 and , 1022) and 7.9% high (H)-MRD ($ 1022), compared to 7.4% uMRD, 17.1% L-MRD, 26.9% H-MRD in the ClbG arm. No difference has been observed (HR 1.027, 95% CI 0.602- 1.753, p = 0.921) for overall survival; median overall survival has not been reached in either group. Second primary malignancies were reported in 36 (17%) patients in the VenG arm and 22 (10.3%) in the ClbG arm. No new safety signals were observed. Conclusions: The results suggest that the superior efficacy and deep remissions after fixed-duration VenG are maintained during extended follow-up, and show the long-term benefits of 12 cycles of VenG across all known risk categories. Clinical trial information: NCT02242942. Research Sponsor: F. Hoffmann–La Roche and AbbVie.

8028 Poster Session (Board #361), Fri, 8:00 AM-11:00 AM

Impact of premature venetoclax (Ven) discontinuation/interruption on outcomes in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL): Phase III MURANO study results.

Anthony R. Mato, Jeff P. Sharman, Juliana Biondo, Mei Wu, Yong Mun, Su Young Kim, Kathryn Humphrey, Michelle Boyer, Qian Zhu, John F. Seymour; Center for CLL, Memorial Sloan Kettering Cancer Center, New York, NY; Willamette Valley Cancer Institute and US Oncology Research Center, Eugene, OR; Genentech, Inc., South San Francisco, CA; AbbVie Inc., North Chicago, IL; Roche Products Limited, Welwyn Garden City, United Kingdom; Peter MacCallum Cancer Centre, Royal Melbourne Hospital, The University of Melbourne, Melbourne, Australia

Background: Ven + rituximab (VenR) has a manageable safety profile and improves survival in patients (pts) with R/R CLL, but discontinuation/interruption is frequent. We present new data from the Phase III MURANO study on the impact of Ven early discontinuation/interruption on outcomes in pts with R/R CLL. Methods: Time-dependent Cox proportional hazards regression models, stratified by 17p deletion and risk status, evaluated the impact of Ven discontinuation/interruption on investigator-assessed PFS and OS. Analyses were performed retrospectively (without type-1 error control) in intent-to-treat pts with R/R CLL from the fixed-duration VenR arm of MURANO (NCT02005471; data cut-off: May 8, 2019). Results: 140/194 pts (72%) in the VenR arm completed 2 years of therapy. Early discontinuation occurred in 54/194 (28%) pts (adverse events [AEs]: 29, disease progression [PD]: 12, withdrawal: 5, physician decision: 3, death: 2, other: 2, non-compliance: 1). Median Ven durations for pts discontinuing due to AEs and PD: 11.3 (0.5–24.6) and 17.1 (4.6–25.1) months, respectively (p = 0.08). Inferior PFS was observed in pts who discontinued Ven early for any reason except PD or due to AEs, versus those who completed therapy (Table). Greater cumulative Ven exposure significantly reduced risk of a PFS/OS event (PFS: HR 0.93, 95% CI 0.88–0.99, p = 0.0168; OS: HR 0.85, 95% CI 0.79–0.92, p , 0.0001). Treatment interruption for AEs occurred in 134/194 (69%) pts, most commonly due to neutropenia (84/194; 43%), per protocol requirements. Median duration of interruption: 9 (1–93) days. Treatment interruption, regardless of duration, had no impact on PFS or OS (Table). 36 (19%) pts with interruptions later discontinued Ven. Conclusions: In MURANO, early Ven discontinuation was associated with suboptimal outcomes; Ven interruption was not. These data highlight the importance of effective control of toxicity to realize the full benefit of VenR treatment. Clinical trial information: NCT02005471. Research Sponsor: Genentech and AbbVie provided finan- cial support for the study. Third-party medical writing assistance, under the direction of authors was provided by Rachel Dobb of Gardiner-Caldwell Communications, and was funded by F. Hoffmann-La Roche Ltd.

Impact of early Ven discontinuation/interruption on PFS and OS. Ven PFS HR (95% CI) p-value OS HR (95% CI) p-value Early discontinuation Any* (n = 181) 5.98 (3.31–10.82) , 0.0001 –– Due to AE (n = 174) 5.82 (2.39–11.57) , 0.0001 –– Interruption†‡ Any 0.67 (0.38–1.19) 0.17 0.97 (0.43–2.21) 0.95 ‡8 days 1.01 (0.59–1.72) 0.97 1.35 (0.60–3.02) 0.46 ‡14 days 0.92 (0.51–1.65) 0.77 1.47 (0.63–3.45) 0.37 ‡21 days 0.82 (0.41–1.65) 0.58 1.31 (0.46–3.73) 0.62 *Except PD; †PFS n = 165, OS n = 194; ‡Consecutive days

8029 Poster Session (Board #362), Fri, 8:00 AM-11:00 AM

Brentuximab vedotin and bendamustine as first-line treatment of Hodgkin lymphoma in the elderly (HALO Trial).

Jean Marc Schiano de Colella, Simonetta Viviani, Davide Rapezzi, CATERINA PATTI, Lauriane Clement Filliatre, Andrea Rossi, Fontanet Bijou, Maria Cantonetti, Cecile ´ Borel, Brice Thamphya, Renaud Schiappa, Emmanuel Chamorey, Colin Debaigt, Lauris Gastaud, Antoine Thyss, Andrea Gallamini; Institut Paoli-Calmettes, Marseille, France; European Institute of Oncology, Milan, Italy; Ospedale S. Croce e Carle Cuneo, Cuneo, Italy; Aoor Villa Sofia Cervello, Palermo, Italy; CHU de Nancy, Nancy, France; Asst Papa Giovanni XXIII Bergamo, Bergamo, Italy; Institut Bergonie, ´ Bordeaux, France; Fondazione Poli- clinico Tor Vergata, Rome, Italy; Institut Universitaire du Cancer de Toulouse, Toulouse Cedex, France; Centre Antoine Lacassagne, Nice, France; Biostatistics’ Unite, Antoine Lacassagne Cancer Center, University of Cote d’Azur, Nice, France; Antoine-Lacassagne Cancer Center, Nice, France

Background: Hodgkin Lymphoma (HL) treatment in the elderly is a challenge, as standard ABVD is able to cure no more than 60% of the patients (p.). Bendamustine (Be), and Brentuximab Vedotin (BV), are well-tolerated and effective drugs in relapsing HL, but only preliminary data exist in 1st line treatment of the elderly (Evens AM 2018). Methods: HALO is a prospective international multicenter open-label phase I/II study (NCT02467946) to assess the safety and efficacy of Be-BV in advanced-stage elderly HL p. Briefly, BV 1.2 mg/kg on D1, and Be 90 mg/m2 on D1-2 were administered Q3W for 6 cycles. The primary endpoint was the feasibility and the efficacy of Be-BV. Results: Between July 2015 and February 2019, 59/60 p. consecutive enrolled received at least 1 Be-BV cycle, and are valuable for primary endpoint. One p. was excluded because a histological review showing angioimmunoblastic T- Cell Lymphoma. The mean age was 70.32 (62-79), and M/F ratio 41/18. The Ann-Arbor stage was IIB in 12, III in 14 and IV in 33 patients, B-symptoms (y/n) 40/19. IPS was 0-2 in 19 and $ 3 in 40 p., P.S. (ECOG) was 0-1 in 53, 2 in 6 p., nonetheless most of them were frail, as ADL was $ 6 in 47 (79%) and IADL was $ 8 in 42 (71%) p. Most frequent co-morbidities were cardio-vascular disease (45) metabolism disorders (31) prostatic adenoma (11). 163 treatment-related adverse events (WHO 3-4) were recorded: neutropenia and lymphopenia, (134), infections (7), cutaneous reactions (5), liver toxicity (2). No case of grade . 2 peripheral neuropathy was recorded. Out of 59 p., 41 concluded and 18 interrupted the treatment for toxicity (8), progression (5), treatment failure (2), CMV reactivation (3). The latter was recorded in 17 p., 12/17 received valgancyclovir. 4 p. died with CMV viremia. After a mean follow-up of 20.6 (0.3-46.5) months, 37/59 (63%) were in CR, while 22 (37%) have progressed (5) or relapsed (17). The 2-y OS and PFS in ITT analysis were 83% (95% CI 71-96) and 54% (95% CI 41-72) and in PP 89% (95%CI 75-100) and 78% (95%CI 64-96), respectively. 22 p. had a PFS event: 5 progression (2 deaths), 17 relapse (8 deaths). 10 p. died for recurrent HL (5), sepsis (1), secondary malignancy (2), respiratory insufficiency (1) and unknown (1). Conclusions: The Be-BV combination, a novel anthracycline-free regiment for first line treatment of HL in elderly, proved effective in unse- lected, frail, poor-risk, HL p. aged more than 60 in daily hospital real life. The CMV reactivation is frequent and should be treated with preemptive antiviral therapy upon detection of CMV DNA in plasma. Clinical trial information: NCT02467946. Research Sponsor: TAKEDA MILLENIUM.

8030 Poster Session (Board #363), Fri, 8:00 AM-11:00 AM

Effect of antibiotic use prior to or concurrent with immune checkpoint inhibitors on outcomes in patients with Hodgkin lymphoma.

Steven R Hwang, Alexandra Higgins, Betsy LaPlant, Matthew J. Maurer, Stephen M. Ansell, Gita Thanarajasingam, N. Nora Bennani; Department of Internal Medicine, Mayo Clinic, Rochester, MN; Division of Hematology, Mayo Clinic, Rochester, MN; Mayo Clinic, Rochester, MN; Department of Biostatistics, Mayo Clinic, Rochester, MN

Background: There is growing interest in the identification of modifiable patient-specific factors that may predict response to immune checkpoint inhibitors (ICIs) in classical Hodgkin lymphoma (cHL). Recently, it has been proposed that antibiotic use could decrease the efficacy of ICIs in the treatment of advanced solid malignancies. The objective of our study is to assess whether antibiotic use prior to or concurrent with ICIs is associated with changes in outcomes in patients with cHL. Methods: Patients who received a PD-1 or CTLA-4 blocker for the treatment of cHL at Mayo Clinic Rochester between January 1, 2011 and October 20, 2018 were identified. We conducted a longitudinal retrospective chart review to identify those who received antibiotics within 30 or 90 days prior to initiation or concurrent with ICI therapy. Univariate cox regression analysis was used to assess for an association between antibiotic use and overall survival (OS) and progression-free survival (PFS) within these groups; a time-dependent variable was used for concurrent antibiotic use. Results: A total of sixty-two patients were identified (61% male, median age at ICI initiation 35 years [range: 19-87]). Median duration of follow up from ICI start was 38 months (range: 4-78). Twenty-one patients (34%) received antibiotics within 90 days of initiation of ICI, of which thirteen (21%) received antibiotics within 30 days. Thirty-five patients (57%) received antibiotics concurrently with ICI. Concurrent and prior antibiotic use within 90 days of ICI were both associated with inferior PFS (concurrent HR = 6.38 [95% CI 3.02-13.47]; 90-day HR = 2.21 [95% CI 1.10-4.47]) and OS (concurrent HR = 8.77 [95% CI 1.91- 40.36]; 90-day HR = 2.96 [95% CI 1.09-8.04]). Conclusions: Antibiotic use is associated with inferior outcomes in patients with cHL treated with ICIs in this single institution cohort. This may reflect potential antibiotic effects on the gut microbiome (GMB) and immune system as has been suggested in prior studies. Further confirmatory studies and examination of potential confounding covariates are needed. Research Sponsor: U.S. National Institutes of Health.

8031 Poster Session (Board #364), Fri, 8:00 AM-11:00 AM

Outcome of elderly patients with classical Hodgkin lymphoma (HL) in British Columbia.

Phoebe Tsz Man Cheng, Diego Villa, Alina S. Gerrie, Ciara L Freeman, Graham W Slack, David W. Scott, Joseph M. Connors, Laurie Helen Sehn, Kerry J. Savage; Department of Medicine, University of British Columbia, Vancouver, BC, Canada; British Columbia Cancer Centre for Lymphoid Cancer, Vancouver, BC, Canada

Background: Outcomes in elderly patients (pts) with Hodgkin lymphoma (HL) have traditionally been poor. We evaluated the survival of elderly pts (.60 years [y]) with classical HL in British Columbia (BC). Methods: All pts aged .60 y newly diagnosed with classical HL from 1961 to 2019 were identified in the BC Cancer Lymphoid Cancer Database. Limited stage was defined as non-bulky (,10 cm) stage 1A/ IB or 2A (before 2000 1B = advanced stage), with the remainder considered advanced stage. Results: Following exclusions (HIV positive n=4, incomplete data n=21, prior or concurrent other lymphopro- liferative disease n=67), 713 pts were identified. With a median follow up of 6.0 y (0.1 - 24.0 y) in living pts, there has been an improvement in 5 y DSS/OS (both p,.001) by decade comparison: 1960s (n=52) 25%/17%; 1970s (n=75) 38%/31%; 1980s (n=90) 51%/43%; 1990s (n=115) 53%/42%; 2000s (n=180) 66%/57%; 2010s (n=201) 63%/53%. To account for advances in diagnosis, staging, supportive care, and therapy in the modern era, we evaluated the outcome of pts diagnosed since 01/ 1995. A total of 368 pts were treated with curative intent (Table). Most pts received multi-agent chemotherapy (n=359, 98%: ABVD[like] n=351, alkylator-based n=7, CHOP n=1), 8 pts had radiotherapy (RT) alone, and 1 pt had surgery (primary CNS HL). The 5 y DSS, PFS, and OS were 74%, 57%, and 62%, respectively. Increasing age was associated with inferior outcomes (5 y DSS/PFS/OS): 61- 70 y (81%/70%/74%), 71-80 y (69%/47%/52%), and .80 y (59%/27%/31%) (DSS p=.011; PFS p,.0001; OS p,.0001). Of 318 pts that received bleomycin, 60 (19%) developed pulmonary toxicity, including 22 cases that occurred after cycles 1 and 2. Overall, 24/368 pts (7%) died of acute treatment toxicity (pulmonary [bleomycin n=10, radiation n=1], infection n=10, cardiac n=3). There was no association between age and developing bleomycin (p=.80) or lethal treatment toxicities (p=.74). Conclusions: The outcome of elderly pts with HL has improved in recent decades. However, treatment related toxicity remains a concern and use of multi-agent chemotherapy, particularly bleomycin- containing regimens, should be undertaken with caution. Research Sponsor: None.

Clinical features of HL patients treated with curative intent in the modern era (1995 – present). Clinical feature Pts, n=368 (%) Age, y - Median (range) 70 (61-92) 61-70 199 (54) 71-80 128 (35) >80 41 (11) Advanced stage 255/365 (70) Male 212 (58) ECOG PS >1 132/360 (37) Mass >10 cm 32/339 (9) Subtype - Nodular sclerosis 177 (48) Not classifiable 90 (24) Mixed cellularity 72 (20) Lymphocyte rich 22 (6) Lymphocyte depleted 7(2)

8032 Poster Session (Board #365), Fri, 8:00 AM-11:00 AM

Frontline brentuximab vedotin as monotherapy or in combination for older Hodgkin lymphoma patients.

Christopher A. Yasenchak, Rodolfo Eduardo Bordoni, Dipti Patel-Donnelly, Tim Larson, Jerome H. Goldschmidt, Ralph V. Boccia, Vivian Jean M. Cline, Andres Forero-Torres, Robert Brownell Sims, Trevor Newhook, Jonathan W. Friedberg; Willamette Valley Cancer Institute and Research Center/US Oncology Research, Eugene, OR; Georgia Cancer Specialists, Marietta, GA; Virginia Cancer Specialists, Fairfax, VA; Minne- sota Oncology/The US Oncology Network, Minneapolis, MN; Oncology and Hematology Assoc of SW Virginia, Blacksburg, VA; Center for Cancer and Blood Disorders, Bethesda, MD; Texas Oncology-Round Rock Seton Williamson, Round Rock, TX; Seattle Genetics, Bothell, WA; Seattle Genetics Inc., Bothell, WA; University of Rochester Medical Center, Rochester, NY

Background: Older patients with classical Hodgkin lymphoma (cHL) have poor outcomes relative to younger patients, often due to comorbidities and toxicities related to standard first-line (1L) chemotherapy (5-yr PFS: 30%–45% vs 75%–80%) (Evens 2008; Proctor 2009). Brentuximab vedotin (BV, ADCETRIS®), a CD30-directed antibody-drug conjugate, has robust activity in patients refractory to several lines of chemotherapy. Methods: This phase 2, open-label study, SGN35-015 (NCT01716806), evaluated efficacy and tolerability of BV alone or combined with single-agents in treatment-naive cHL patients $60 yr. The full-analysis set (FAS) includes all patients who received BV (1.8 mg/kg IV). Patients in Part A received BV monotherapy on Day 1 of every 3-week cycle (n = 26); Part B: BV+dacarbazine (DTIC; 375 mg/m2; n = 19); Part C: BV+bendamustine (benda; 70 mg/m2; n = 20); and Part D: BV+nivolumab (nivo; 3 mg/kg; n = 20). The efficacy evaluable (EE) set includes all patients who had at least 1 post-baseline response assessment (n = 25, 19, 17, 19). Results: Demographic characteristics were generally similar: median age 78, 69, 75, and 72 yr in Parts A, B, C, and D, respectively, and 62% of patients (range 45%–70%) reported impaired physical functioning at baseline. Most patients had disease stage III/IV (62%, 68%, 75%, 80%), were ECOG 0/1 (77%, 74%, 80%, 95%), and male (54%, 68%, 50%, 75%). Median time from diagnosis was 1.2 to 1.5 mo (FAS; 10 Jan 2019 data cutoff). ORR were high (92%, 100%, 100%, 95%) at a median follow-up of 59.4, 58.6, 51.3, and 19.4 mo in the EE data set. Median OS in the FAS set was 77.5 mo with monotherapy; 64.0, 46.9, and not reached in the combination parts. Treatment-related AE $ Grade 3 occurred in 50%, 37%, 70%, and 60% of patients; peripheral neuropathy (PN) was most common (35%, 26%, 20%, 35%). Treatment-related SAEs occurred in 12%, 11%, 40%, and 5% of patients. Part C enrollment (BV+benda) closed early due to multiple acute toxicities. There were no treatment-related deaths in any part of the study. The median treatment cycles per patient were 8.0, 12.0, 5.0, and 14.5. Treatment discontinuation due to related AEs occurred in 42%, 42%, 40%, and 30% of patients, most commonly due to PN (38%, 37%, 30%, 20%). Conclusions: Older patients with cHL and multiple comorbidities have very high response rates with BV as monotherapy or combined with other single agents and improved tolerability versus combination chemotherapy. Median overall survival exceeded 6 yr with BV monotherapy. BV+nivo or BV+DTIC appeared to be the most reasonable combination treatment options in this study. Clinical trial information: NCT01716806. Research Sponsor: Seattle Genetics.

8033 Poster Session (Board #366), Fri, 8:00 AM-11:00 AM

Gls-010, a novel anti-PD-1 mAb in Chinese patients with relapsed or refractory classical Hodgkin lymphoma: Preliminary impressive result of a phase II clinical trial.

Yuqin Song, Jun Zhu, Ningjing Lin, Mingzhi Zhang, Hai Bai, Hui Liu, Jie Cui, Xiaoyan Ke, Huilai Zhang, Lihong Liu, Dongmei Yan, Yongsheng Jiang, Aimin Zang, Junyuan Qi, Li Wang, Zhuogang Liu, Bing Xu, Ying Zhang, Zhihui Zhang, Haijin Meng; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), the Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China; The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; 940 Hospital of the Joint Logistic Support Force of the PLA, Lanzhou, China; Beijing Hospital, Beijing, China; The Cancer Hospital of Gansu Province, Lanzhou, China; Peking University Third Hospital, Beijing, China; Tianjin Medical University Cancer Institute & Hospital, Tianjin, China; Fouth Hospital of Hebei Medical University,Tumor Hospital of Hebei Province, Shijiazhuang, China; The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China; Tongji Hospital, Tongji Medical College Huangzhong University of Science & Technology, Wuhan, China; The Affiliate Hospital of Hebei Medical University, Baoding, China; The Hematology Hospital, Chinese Academy of Medical Sciences, Tianjin, China; The People’s Hospital of Jiangsu Province, Nanjing, China; Shengjing Hospital of China Medical University, Shenyang, China; The First Affiliated Hospital of Xiamen University, Xiamen, China; Affiliated Hospital of Guangdong Medical University, Zhanjiang, China; Sichuan Cancer Hospital&Institute, Chengdu, China; Guangzhou Gloria Biosciences Co., Ltd., Beijing, China

Background: classical Hodgkin lymphoma (cHL) are characterized by genetic alterations at the 9p24$1 locus and PD-L1 ligand overexpression. GLS-010 is a novel fully human anti-PD-1 mAb and exhibited favorable result in previous Phase I study. This multi-center, single-arm Phase II clinical trial is aimed to further evaluate the safety and efficacy profile of GLS-010 in Chinese patients (pts) with relapsed or refractory cHL. Methods: All pts enrolled received GLS-010 240mg every 2 weeks until disease progression, death, unacceptable toxicity or withdraw from the study. The primary endpoint was objective response rate (ORR) by independent review committee (IRC) per Lugona 2014. Adverse events (AEs) were graded by NCI CTCAE v4.03. Results: 85 pts with relapsed or refractory cHL who had received at least 2 lines of prior systemic chemotherapies were enrolled and treated. As of August 2 2019, data cutoff, pts received a median of 8 treatment cycles (1 cycle include 2 injections), with 12 pts discontinued and 73 pts were still in treatment. At a median follow-up of 6.57 months, an ORR was reported in 78 of 85 patients (91.76%, 95%CI, 83.77-96.62), by an IRC assessment, including 30(35.3%) pts with a complete response (CR) and 48 pts (56.5%) with a partial response (PR). Median duration of response (DoR) and progression free survival (PFS) were not reached yet. Treatment-related adverse events (TRAEs) of any grade occurred in 77 (90.6%) of 85 patients, most of which were Grade 1-2.The most common TRAEs were fever (26/85, 30.6%), neutrophil count decreased (16/85, 18.82%), white blood cell count decreased (15/85, 17.65%). $ Grade 3 TRAEs occurred in 23 (27.06%) pts, most commonly, hepatic function abnormal (5/85, 5.88%), hyperuricaemia (4/85, 4.71%). Conclusions: GLS-010 showed impressive anti-tumor activity (ORR = 91.96%) and manageable safety profile in Chinese patients with relapsed or refractory cHL, which could be a new safe and effective treatment option in this setting. Clinical trial information: NCT03655483. Research Sponsor: Guangzhou Gloria Biosciences Co,. Ltd.

8034 Poster Session (Board #367), Fri, 8:00 AM-11:00 AM

Sintilimab for relapsed/refractory classical Hodgkin’s lymphoma: Long-term follow-up on the multicenter, single-arm phase II ORIENT-1 study.

Hang Su, Yongping Song, Wenqi Jiang, Xiuhua Sun, Wenbin Qian, Wei Zhang, Yuhuan Gao, Zhengming Jin, Jianfeng Zhou, Chuan Jin, Liqun Zou, Lugui Qiu, Wei Li, Jianmin Yang, Ming Hou, Shan Zeng, Peng Liu, Yuankai Shi, Hui Zhou, Hongli Zuo; The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China; The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China; State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China; Department of Oncology, Second Hospital of Dalian Medical University, Dalian, China; The First Affiliated Hospital of Medical School of Zhejiang Uni- versity, Hangzhou, China; Peking Union Medical College Hospital, Beijing, China; Fouth Hospital of Hebei Medical University,Tumor Hospital of Hebei Province, Shijiazhuang, China; The First Affiliated Hospital of Soochow University, Suzhou, China; Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; The Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, China; West China Hospital of Sichuan University, Chengdu, China; Institute of Hematology & Blood Diseases Hospital,Chinese Academy of Medical Sciences, Tianjin, China; The First Bethune Hospital of Jilin University, Jilin, China; ChangHai Hospital, Shanghai, China; Qilu Hospital of Shandong University, Jinan, China; Department of Oncology, Xiangya Hospital, Central South University, Changsha, China; Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, China; Innovent Biologics, Inc., Suzhou, China; Innovent Biologics, Inc., Beijing, China

Background: Sintilimab, a programmed death-1 checkpoint inhibitor, has demonstrated efficacy in relapsed/refractory cHL after the primary analysis of the ORIENT-1 study. Here, we report the updated safety and efficacy profile after long-term follow-up. Methods: ORIENT-1 is a multicenter, single-arm, phase II study in China. Classical Hodgkin’s lymphoma patients who had failed $2 lines of systemic therapy, including autologous hematopoietic stem cell transplantation (HSCT) were enrolled. Sinti- limab, 200 mg IV was given every 3 weeks, until disease progression, death, unacceptable toxicity, or withdrawal from study. The primary endpoint objective response rate (ORR) by an independent radiological review committee (IRRC) per IWG 2007 has been reported before. The progression free survival (PFS) by IRRC follow-up data are reported herein. Results: 96 patients were treated. As of the data cutoff on 30 Sep, 2019, 57.3 % patients complete two-year treatment, with a median follow-up of 26.7 months. The median duration of treatment was 24.1 months (range: 0.7 to 24.8). Of 49 patients with progressive disease (PD) by investigator, 39/49 (79.6%) patients received treatment beyond PD, with a median treatment duration after PD of 8.0 months (range: 1.4 to 20.8). The median PFS was 18.6 months (95%CI: 14.4 to 22.3). Median overall survival has not been reached. Two-year OS rate was 96.3% (95%CI: 88.9% to 98.8%). The treatment-related adverse event (TRAE) was reported in 92/96 (95.8%) patients, most (71/96, 74.0%) of which were grade 1-2. The most common grade 3 or 4 TRAEs were pyrexia (3/96, 3.1%), lipase increased (3/96, 3.1%) and lymphocyte decreased (3/96, 3.1%). Conclusions: The results from long-term follow-up showed that, in addition to a high rate of response, sintilimab also demonstrated durable efficacy and favorable long-term safety profile. Con- sidering the high rate (nearly 80%) of treatment beyond PD, IWG 2007 which was used to evaluate PFS may not be a suitable criteria for evaluating the efficacy of anti-PD-1 antibody in cHL. Further investigation and analysis are required. Clinical trial information: NCT03114683. Research Sponsor: Innovent Biologics, Inc., China National Major Project for New Drug Innovation (2017ZX09304015 and 2018ZX09301014009) and CAMS Innovation Fund for Medical Sciences (CIFMS) (2016-I2M-1- 001)

8035 Poster Session (Board #368), Fri, 8:00 AM-11:00 AM

Mantle cell lymphoma: initial report from the North American Mantle Cell Lymphoma Consortium.

Kai Fu, Guohua Yu, Chengfeng Bi, Hongxia Cheng, Lynette Smith, Ji Yuan, Hina Naushad, Brian K. Link, Craig R. Nichols, Paul M. Barr, Brad S. Kahl, Douglas Stewart, Stefan K Barta, Anne Beaven, Ranjana H. Advani, Peter Martin, Timothy Greiner, Dennis Weisenburger, James O. Armitage, Julie Vose; University of Nebraska Medical Center, Omaha, NE; UNMC, Omaha, NE; Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE; University of Iowa Carver College of Medicine, Iowa City, IA; Testicular Cancer Commons and SWOG Group Chair’s Office, Portland, OR; University of Rochester Medical Center, Rochester, NY; University of Wisconsin Carbone Cancer Center, Madison, WI; Tom Baker Cancer Center, Calgary, AB, Canada; Fox Chase Cancer Center, Philadelphia, PA; Duke University Medical Center, Durham, NC; Stanford University, Stanford, CA; Weill Cornell Medicine, New York Presbyterian Hospital, New York, NY; City of Hope, Duarte, CA

Background: The goal of the North American Mantle Cell Lymphoma (MCL) Project is to evaluate the clinical, biological, and genomic markers that affect the outcome of patients with MCL. Methods: We have retrospectively studied the clinical and pathological features of 307/421 patients diagnosed with MCL between January 2000 to December 2012 from 23 institutions across North American. Results: The male to female ratio of MCL patients was 3.5:1, with a median age of 66 years (range: 24-106 years). Approximately 29% of patients (78/269) presented with B symptoms and 257 (257/307, 83.7%) patients had extranodal involvement at diagnosis. Median follow-up was 7.1 years (range, 0.03 to 16.6 years) with the five-year PFS and OS at 27.8%, and 54.4%, respectively. Univariate analysis revealed that the following factors were significantly associated with both inferior OS and PFS (p, 0.05): older age ($60 years), presence of B symptoms, advanced Ann Arbor stage, elevated LDH, low platelets (#100K/ml), blastoid/pleomorphic cytology, Ki67 proliferation $30%, circulating tumor cells, no transplantation (vs. transplantation), and allogeneic (vs. autologous) stem cell transplantation. In addition, large tumor size (maximal diameter . 3cm), high WBC ( . 103103/ml), CD5 or CD23 positivity, and a complex karyotype were associated with inferior OS (p, 0.05). Multivariate Cox regression analysis showed age ($ 60y; p= 0.0028, HR = 2.44, 95% CI: 1.36-4.38) and high LDH (p= 0.0062, HR = 2.19, 95% CI: 1.25-3.84) were the two factors predicting the clinical outcome. MIPI- c, a commonly used prognostic scoring system which includes Ki67, stratified the 100 MCL cases into four group with distinct clinical outcomes (p, 0.001). Using readily-available clinical and pathological variables, we developed a simple and robust scoring system, MIPI-P (pathology), which consisted of age ($60 years), LDH (high), Ki67 index ($30%), Ann Arbor stage (III/IV), and cytological type (blastoid/ pleomorphic), each contributing one point. The MIPI-P system stratified 104 MCL cases into three distinct groups (p, 0.001). Median survival for the different groups were: low grade (0-1 points): 11.8 years; intermediate grade (2-3 points): 4.9 years; and high grade (4-5 points): 1.6 years. We further validated this system in an independent cohort of 33 MCL cases and confirmed that the modified MIPI- P provided robust prognostic predication (p= 0.014). Conclusions: The clinical and biologic characteristics of MCL can provide information assisting with the prognosis of patients with MCL. Research Sponsor: University of Nebraska Foundation.

8036 Poster Session (Board #369), Fri, 8:00 AM-11:00 AM

Clinical activity of cirmtuzumab, an anti-ROR1 antibody, in combination with ibrutinib: Interim results of a phase Ib/II study in mantle cell lymphoma (MCL) or chronic lymphocytic leukemia (CLL).

Hun Ju Lee, Michael Y. Choi, Tanya Siddiqi, William G. Wierda, Jacqueline Claudia Barrientos, Nicole Lamanna, Alec Goldenberg, Iris Isufi, Joseph M. Tuscano, Suki Subbiah, Elizabeth Kristine Weihe, Xen Ianopulos, James Bradley Breitmeyer, Frank J. Hsu, Michael Wang, Catriona HM Jamieson, Thomas J. Kipps; The University of Texas MD Anderson Cancer Center, Houston, TX; University of California San Diego Moores Cancer Center, San Diego, CA; City of Hope National Medical, Duarte, CA; Hofstra Northwell School of Medicine, Hempstead, NY; New York-Presbyterian, Columbia University Medical Center, Manhasset, NY; NYU Langone Medical Center, New York, NY; Yale School of Medicine, New Haven, CT; UC Davis, Sacramento, CA; Tulane Univ School of Medicine, New Orleans, LA; Oncternal Therapeutics, Inc, San Diego, CA

Background: ROR1 is an onco-embryonic tyrosine kinase receptor that is re-expressed at high levels on many hematologic and solid cancers but not on normal adult tissues. ROR1 binds Wnt5a, resulting in increased tumor growth and survival, cancer cell stemness and epithelial mesenchymal transition. Cirmtuzumab (Cirm) is a humanized monoclonal antibody designed to inhibit the tumor promoting activity of ROR1. In this study, we examined the safety and efficacy of Cirm in combination with ibrutinib (Ibr) in MCL or CLL. Methods: As of Jan 29, 2020, 12 pts with relapsed refractory (RR) MCL were enrolled into Part 1 Dose Escalation (DE). All MCL pts had stage 3/ 4 at original diagnosis, 25% had bulky tumor at study entry, 58% had intermediate/high risk MIPI scores and the majority (83%) had $ 2 prior regimens. 34 pts with CLL [12 treatment na¨ıve (TN) and 22 RR pts] enrolled into Part 1 DE (n = 18) or Part 2 Expansion (n = 16). At least 79% of CLL pts were high risk as determined by unmutated IGHV, 17p/p53 loss, and/or del 11q. DE pts received Cirm IV q2wks x 3-5 doses then q4wks plus Ibr (starting D28). Following DE, Cirm 600mg IV q2wks x3 then q4wks plus Ibr (420mg/day CLL or 560mg/day MCL) was chosen for Expansion. Results: Safety: only grade 1/ 2 AEs were reported as possibly related to Cirm alone, whereas the safety profile attributed to Ibr or Ibr / Cirm was similar to published data, with no new or unexpected events. Efficacy for MCL: 83% ORR, 33% (4) CR, 50% (6) PR, 17% (2) SD. CRs were achieved at a median of 3.6 mos in heavily pretreated pts, including 2 with bulky disease . 5cm. Prior therapy of the 4 CR pts: 2 pts failed R-Ibr (7-10 mos) and R-hyperCVAD, 1 pt, auto-SCT and allo-SCT, 1 pt, auto-SCT and CAR-T. Efficacy for CLL: 88% ORR (92% TN, 86% RR), 3% (1) CR, 85% (22) PR/ (7) PR-L, 12% (4) SD. In addition, 3 PR pts with CLL met criteria for “Clinical CR, bone marrow biopsy not performed”. The pt achieving a CR had RR disease with del 11q; this pt remains in remission . 6 mos after stopping all therapy. At a median follow-up of 9.9 mos, 100% of CLL pts are free of disease progression and . 82% remain on study. Conclusions: Cirm in combination with Ibr is a well-tolerated and active regimen for RR MCL and TN or RR CLL. In this evaluation of 46 pts, the ORR and PFS continue to improve with longer follow-up and additional pts, supporting continued investigation of this regimen in ROR1 expressing tumors. This study is ongoing and enrolling an Expansion arm for MCL pts and an open-label randomized Phase 2 in CLL pts comparing Ibr alone to Cirm /Ibr. Clinical trial information: NCT03088878. Research Sponsor: California Institute for Re- generative Medicine (CIRM) grant, Pharmaceutical/Biotech Company.

8037 Poster Session (Board #370), Fri, 8:00 AM-11:00 AM

Outpatient treatment with lisocabtagene maraleucel (liso-cel) across a variety of clinical sites from three ongoing clinical studies in relapsed/refractory (R/R) large B-cell lymphoma (LBCL).

Carlos R. Bachier, John E. Godwin, Charalambos Andreadis, Maria Lia Palomba, Jeremy S. Abramson, Alison R. Sehgal, Gerhard Hildebrandt, Don A. Stevens, Daanish Hoda, Edward J. Licitra, Tanya Siddiqi, Thalia Andrea Farazi, Ana Kostic, Nikolaus S. Trede, Lei Wang, James Lymp, David G. Maloney; Sarah Cannon Blood Cancer Network, Nashville, TN; Providence Portland Medical Center, Portland, OR; University of California at San Francisco, San Francisco, CA; Memorial Sloan Kettering Cancer Center, New York, NY; Massachusetts General Hospital, Boston, MA; University of Pittsburgh Medical Center, Pittsburgh, PA; University of Kentucky, Lexington, KY; Norton Cancer Institute, Louisville, KY; Intermountain Medical Center, Salt Lake City, UT; Regional Cancer Care Associates, East Brunswick, NJ; City of Hope Cancer Center, Duarte, CA; Juno Therapeutics, a Bristol- Myers Squibb Company, Seattle, WA; Juno Therapeutics, a Bristol-Myers Squibb company, Seattle, WA; Fred Hutchinson Cancer Research Center, Seattle, WA

Background: Currently approved CAR T cell therapies are generally administered as inpatient (inpt) treatment at university medical centers due to concerns about frequency, onset, severity, and management of AEs, including cytokine release syndrome (CRS) and neurologic events (NEs). We sought to characterize whether patients (pts) could be safely monitored in the outpatient (outpt) setting after receiving liso-cel, an investigational, CD19-directed CAR T cell product administered at equal target doses of CD8+ and CD4+ CAR+ T cells, across university and non-university sites in TRANSCEND NHL 001 (NCT02631044), OUTREACH (NCT03744676), and PILOT (NCT03483103). Methods: Eligible pts had R/R LBCL after systemic chemoimmunotherapy; moderately impaired organ function was allowed. For outpt infusion of liso-cel, pts were required to receive safety monitoring education, have a caregiver and stay within 1 h travel to site of care for 30 d post-treatment. All study sites had a multidisciplinary CAR T cell team and standard operating procedures for toxicity monitoring and management. Results: At data cutoff, 53 pts had received liso-cel on Study Day 1 and were monitored as outpts (university, n = 33; non-university, n = 20), including pts $65 y of age (n = 23) and with high tumor burden (SPD $50 cm2; n = 16). Any grade CRS and NEs were reported in 18 (34%) and 14 pts (26%), respectively. Severe CRS and/or NEs occurred in only 2 pts (4%) and were reversible. Median (range) time to onset of CRS and NEs was 5 (2–9) and 8.5 (3–22) d, respectively. Tocilizumab and/or corticosteroids for treatment of CRS and/or NEs were required in 8 pts (15%). Overall, 30 pts (57%) required hospitalization post-treatment, with a median (range) time to hospitalization post-treatment of 5.5 (2–22) d; 9 pts (17%) were hospitalized Study Day 4 or earlier. Two pts required ICU-level care. There were no grade 5 treatment-emergent AEs. Safety in pts monitored as outpts was comparable across types of sites. Overall response rate was 81% (95% CI, 68–91). Safety and efficacy were consistent with data from inpts across the 3 studies (N = 270). Conclusions: Pts with R/R LBCL were successfully treated with liso-cel and monitored for CAR T cell-related toxicity in the outpt setting across different types of sites. Incidences of severe CRS, NEs, and early hospitalization were low; 43% of pts did not require hospitalization. A larger dataset will be presented, including comparisons of outpts vs inpts and sites of care. Clinical trial information: NCT02631044 (TRANSCEND NHL 001), NCT03744676 (OUTREACH), NCT03483103 (PILOT). Research Sponsor: Juno Therapeutics, a Bristol-Myers Squibb Company.

8038 Poster Session (Board #371), Fri, 8:00 AM-11:00 AM

Relevance of bone marrow biopsies for response assessment in NCTN follicular lymphoma clinical trials.

Sarah C. Rutherford, Jun Yin, Levi Pederson, Betsy LaPlant, Mazyar Shadman, Hongli Li, Michael Leo LeBlanc, Kristie A. Blum, Travis Dockter, Peter Martin, Sin-Ho Jung, Barbara W. Grant, Cara Ann Rosenbaum, Chaitra Shankar Ujjani, Paul M. Barr, Joseph M. Unger, Bruce D. Cheson, Nancy L. Bartlett, Jonathan W. Friedberg, John Paul Leonard; Weill Cornell Medicine, New York, NY; Mayo Clinic, Rochester, MN; Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA; Emory University, Winship Cancer Institute, Atlanta, GA; Duke University School of Medicine, Durham, NC; Vermont Cancer Center, University of Vermont, Burlington, VT; University of Rochester Medical Center, Rochester, NY; Georgetown University Hospital, Washington, DC; Washington University School of Medicine, Siteman Cancer Center, St. Louis, MO

Background: Bone marrow biopsies (BMB) are performed pre/post therapy to confirm complete response (CR) in patients (pts) with lymphoma on clinical trials. We evaluated 2 prior data sets and concluded that BMB impact response assessment in a minority of pts with follicular lymphoma (FL) (Rutherford BJH 2017; Rutherford ASH abstract 1605, 2018). We sought to establish if BMB add value in assessing response or identify distinct progression free (PFS) or overall survival (OS) outcomes in a large, multicenter, multi-trial cohort. Methods: Data were pooled from 7 trials of 580 pts with untreated FL conducted through the Alliance for Clinical Trials in Oncology and SWOG from 2002-2016. The proportion of pts with positive (+) baseline BMB, CR on imaging after treatment, and (+) repeat BMB was calculated using total pts enrolled as the denominator. We tested against the null hypothesis that the proportion was = 10%, the threshold below which BMB would be considered irrelevant for response assessment, versus (vs) the alternative hypothesis that this proportion was , 10%, using 1-sided exact binomial test. Response criteria were CT-based. Imaging was not used to assess BM involvement. Because confirmatory BMB were not completed in all indicated pts, landmark survival analyses compared PFS/OS of pts with CR on imaging and negative (-) BMB vs pts with CR on imaging without repeat BMB. Pts with CR on imaging were categorized as having (-) repeat BMB or no repeat BMB within 60 days of first CR on imaging. PFS and OS were calculated from time of first CR and estimated using Kaplan-Meier and Cox models adjusting for age, sex, stage, Follicular Lymphoma International Prognostic Index (FLIPI) score, and treatment type (targeted vs chemotherapy plus targeted therapy), and stratified by treatment arm. Results: Median age was 55 with 51% male, 96% stage III-IV, and 88% grade I-II. FLIPI scores were 113 low, 265 intermediate, and 199 high risk. 67% received chemotherapy-based regimens. Baseline BMB was (+) in 321 (55%). Only 5/580 (0.8%) had (+) baseline BMB, CR on imaging, and subsequent (+) BMB (p , 0.0001). Of pts with CR on imaging, PFS and OS were not different among pts with (-) BMB vs pts without repeat BMB (PFS: HR = 1.08, 95%CI 0.61-1.93, p = 0.783; OS: HR = 0.52, 95%CI 0.20-1.40, p = 0.199). Conclusions: BMB requirements may discourage pt participation in trials and add pain, expense and time without providing necessary information. We recommend eliminating BMB for response assessment from FL clinical trials. Clinical trial information: NCT00553501, NCT01145495, NCT01190449, NCT01286272, NCT01829568, NCT00822120, and NCT00770224. Research Sponsor: Alliance for Clinical Trials Foundation, https://acknowledgments.alliancefound.org, Pharmaceutical/Biotech Company, U.S. National Insti- tutes of Health, U10CA180821, U10CA180882.

8039 Poster Session (Board #372), Fri, 8:00 AM-11:00 AM

Real-world outcomes of elderly patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) treated with chimeric antigen receptor T-cell (CAR-T) therapy.

Lindsey Fitzgerald, Adam Kittai, Loretta J. Nastoupil, Alexandra Waller, Caron A. Jacobson, Anna Saucier, Manali K. Kamdar, Janet Spradley, Nathan Denlinger, Jonathan Chipman, Boyu Hu; Huntsman Cancer Institute-University of Utah Health Care, Salt Lake City, UT; The Ohio State University Comprehensive Cancer Center, Columbus, OH; The University of Texas MD Anderson Cancer Center, Department of Lymphoma/Myeloma, Houston, TX; The University of Texas MD Anderson Cancer Center, Houston, TX; Dana-Farber Cancer Institute, Boston, MA; Dana Farber Cancer Institute, Boston, MA; University of Colorado School of Medicine, Aurora, CO; The Ohio State University, Department of Internal Medicine, Columbus, OH; Huntsman Cancer Institute-University of Utah Health, Salt Lake City, UT; Huntsman Cancer Institute-University of Utah, Salt Lake City, UT

Background: CAR-T has drastically improved outcomes for R/R DLBCL patients (pts). While CAR-T is now standard of care for the treatment of R/R DLBCL, little is known about its efficacy and toxicity in elderly pts. Methods: We conducted a multi-center retrospective analysis of pts age $ 70 years old with R/R DLBCL treated with either axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel). Pt demographics, tumor characteristics, CAR-T data, survival and toxicity outcomes were collected at the time of T cell infusion and follow up. Comorbidities were measured using the cumulative illness rating score (CIRS) and hematopoietic cell transplantation-specific comorbidity index (HCT-CI). Results: A total of 77 pts were analyzed with a median age of 73 (range, 70-88); 30 (39%) pts were age $75. Most pts received axi-cel (n = 61, 79%). Unfavorable tumor characteristics included 27 (35%) pts with activated B-cell subtype and 12 (16%) with double/triple hit lymphomas. Median CIRS was 8 (range 0-25) and median HCT-CI was 2 (range 0-9) with significantly higher median CIRS and HCT-CI in pts age $75. With a median time to follow up of 5.2 months (m), median progression free survival (PFS) was 12m and median overall survival (OS) was 15.5m. There was no difference in PFS when comparing younger pts (age 70-74) to older pts (age $ 75), but median OS was significantly shorter for older pts (7.8m vs. not reached; hazard ratio [HR] 0.46, CI 0.21-0.98; p = 0.04). In a multivariate analysis (MVA) of PFS adjusting for baseline characteristics, HCT-CI . 2 (HR 0.23, CI 0.07-0.77; p = 0.02) and use of axi-cel (HR 0.07, CI 0.02-0.32; p = , 0.001) were associated with worse PFS. Grade 3/4 (Lee criteria) cytokine release syndrome (CRS) and CAR-related encephalopathy syndrome (CRES) were assessed in MVA adjusting for baseline characteristics. CRS was associated with CIRS $6 (odds ratio [OR] 3.92, CI 1.07-14.3; p = 0.002) and use of axi-cel (OR 44.9, CI 8.20-245.6; p = 0.006). CRES was associated with older age (OR 6.10, CI 1.86-20.0; p = 0.003), CIRS $6 (OR 3.92, CI 1.07-14.3; p = 0.04) and use of axi-cel (OR 44.9, CI 8.2-245.6; p = , 0.0001). Conclusions: Pts age $75 treated with CAR-T had worse OS, but comparable PFS as compared to younger pts. Validated frailty measurements (CIRS) predicted for increased CRS and CRES. Use of axi-cel was associated with worse PFS and increased toxicities in the elderly, but propensity matched scoring analysis will need to confirm this. Additional pts and longer follow up are required to validate these results. Research Sponsor: None.

8040 Poster Session (Board #373), Fri, 8:00 AM-11:00 AM

Lisocabtagene maraleucel (liso-cel) for treatment of second-line (2L) transplant non- eligible (TNE) relapsed/refractory (R/R) aggressive large B-cell non-Hodgkin lymphoma (NHL): Updated results from the PILOT study.

Alison R. Sehgal, Gerhard Hildebrandt, Nilanjan Ghosh, John E. Godwin, Nina D. Wagner-Johnston, Daanish Hoda, Edward J. Licitra, Javier Munoz, Nikolaus S. Trede, Lei Wang, Jerill Thorpe, Leo I. Gordon; University of Pittsburgh Medical Center, Pittsburgh, PA; University of Kentucky Markey Cancer Center, Lexington, KY; Levine Cancer Institute, Atrium Health, Charlotte, NC; Providence Cancer Institute, Portland, OR; The Johns Hopkins Hospital, Baltimore, MD; Intermountain Health- care, Sandy, UT; Regional Cancer Care Associates, East Brunswick, NJ; Banner MD Anderson Cancer Center, Gilbert, AZ; Juno Therapeutics, a Bristol-Myers Squibb Company, Seattle, WA; Juno Therapeutics, a Bristol-Myers Squibb company, Seattle, WA; Northwestern University, Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, Chicago, IL

Background: Patients (pts) with aggressive large B-cell NHL who are R/R after first-line immunochemotherapy and not eligible for high-dose chemotherapy and HSCT have a poor prognosis and no established standard of care. The ongoing, open-label phase 2 PILOT study is the first to assess the safety and efficacy of liso-cel, an investigational, CD19-directed, defined composition, 4-1BB CAR T cell product infused at equal target doses of CD8+ and CD4+ CAR+ T cells, as 2L therapy in TNE pts (NCT03483103). Methods: Eligible pts had aggressive R/R diffuse large B-cell lymphoma NOS (de novo or transformed follicular lymphoma [FL]), high-grade B-cell lymphoma, or FL grade 3B with 1 line of prior therapy containing an anthracycline and anti-CD20 agent. Pts were deemed TNE by meeting $1 criteria: age $70 y, ECOG PS 2, or impaired organ function (DLCO #60% [but SaO2 $92% and CTCAE #1 dyspnea], LVEF $40% to , 50%, creatinine clearance . 30 to , 60 mL/min, or AST/ALT . 2to#5 3 ULN). Liso-cel (100 3 106 CAR+ T cells) was administered 2–7 days after lymphodepletion (LD) with fludarabine/cyclophosphamide. The primary endpoint is ORR; key secondary endpoints are AEs and CR rate. Results: At data cutoff, 25 pts had LD followed by liso-cel infusion. Pt characteristics are summarized in the Table. Overall, 48% (n = 12) had high tumor burden and 48% were primary refractory. 18/25 (72%) pts had grade $3 treatment-emergent AEs, 40% of which were cytopenias. No grade 5 AEs occurred within the first 30 days after liso-cel. Five pts (20%) had cytokine release syndrome (CRS) and 3 (12%) had neurological events (NEs). No grade 3/4 CRS was observed; 2 pts (8%) had grade 3/4 NEs. Five pts (20%) received tocilizumab and/or dexamethasone for CRS/NEs. At a median follow-up of 3.5 mo, the ORR was 80% (95% CI, 59–93; n = 20); 48% of pts (n = 12) achieved CR. Conclusions: These interim data suggest that elderly and/or comorbid pts with R/R aggressive large B-cell NHL, who are not eligible for high-dose chemotherapy and HSCT, can receive 2L liso-cel with similar safety and efficacy to 3L+ pts as previously reported (Abramson, ASH 2019 #241). Updated data with longer follow-up will be presented. Clinical trial information: NCT03483103. Research Sponsor: Juno Therapeutics, a Bristol-Myers Squibb company.

Pt characteristics, n (%) Liso-cel–treated pts (n = 25) Age, y 72 (53–85) Male 16 (64) TNE screening criteria Age ‡70 y 17 (68) ECOG PS 2 7 (28) Organ function 6 (24) ‡2 TNE criteria 6 (24) R/R to last therapy 13 (52)/12 (48) SPD ‡50 cm2/LDH ‡500 U/L 10 (43.5)/5 (20) HCT-CI score, median (range) (n = 24) 2.5 (0–9)

8041 Poster Session (Board #374), Fri, 8:00 AM-11:00 AM

Role of radiotherapy and dose-densification of R-CHOP in primary mediastinal B-cell lymphoma: A subgroup analysis of the unfolder trial of the German Lymphoma Alliance (GLA).

Gerhard Held, Lorenz Thurner, Viola Poeschel, Christian Berdel, German Ott, Christian Schmidt, Andreas Viardot, Peter Borchmann, Ofer Shpilberg, Maike Nickelsen, Massimo Federico, Peter de Nully Brown, Niels Murawski, Lorenz H. Trumper, Heinz Schmidberger, Christian Ruebe, Jochen Fleckenstein, Norbert Schmitz, Markus Loeffler, Marita Ziepert, German Lymphoma Alliance; Department Internal Medicine I, Westpfalzklinikum Kaiserslautern, Kaiserslautern, Germany; Depart- ment Internal Medicine I, Saarland University Medical School, Homburg/Saar, Germany; Department of Radiooncology, Saarland University Medical School, Homburg/Saar, Germany; Insitute of Pathology, Robert-Bosch-Krankenhaus, Stuttgart, Germany; Department of Medicine III, University Hospital Grosshadern/LMU, Munich, Germany; University Hospital of Ulm, Ulm, Germany; Department of Haematology and Oncology, University Hospital of Cologne, Cologne, Germany; Institute of Haematol- ogy, Assuta Medical Centers, Tel Aviv, Israel; Onkologie Lerchenfeld, Hamburg, Germany; Dept of Diagnostic, Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy; Department of Hematology, Rigshospitalet, Copenhagen, Denmark; Universitatsmedizin ¨ G¨ottingen, Goettingen, Germany; Department of Radiooncology, University Medical Center, Mainz, Germany; Department Internal Medicine A, University Medical School, Muenster, Germany; Institute for Medical Informatics, Statistics and Epidemology, University of Leipzig, Leipzig, Germany; Institute for Medical Informatics, Statistics and Epidemology, Leipzig University, Leipzig, Germany

Background: Primary mediastinal B-cell lymphoma (PMBCL) is a distinct entity of aggressive lymphoma, which typically presents in young patients (pts) with a bulky mediastinal mass. Therapy is based on R-CHOP or similar regimens, but the role of treatment intensification and consolidative radiotherapy (RT) is controversial, because data from randomized trials are rare. Methods: The UNFOLDER trial included 18-60 year-old pts (aaIPI = 0 with Bulk [$7.5 cm] or aaIPI = 1) qualifying for radiotherapy to Bulk or extralymphatic involvement (E). Pts were randomized in a 2 x 2 factorial design to 6xR-CHOP- 14 or 6x-R-CHOP-21 without RT or with RT (39.6 Gy) to Bulk and E. Primary endpoint was event-free survival (EFS), secondary endpoints were progression-free (PFS) and overall survival (OS). Response was evaluated by the Internat Standardized Response Criteria, Cheson 1999. Results: 131 PMBCLs were included with a median age of 34 years, 54% were female, 79% had elevated LDH . UNV and 24% had E. 82 pts (R-CHOP-21: 43; R-CHOP-14: 39) were assigned to RT and 49 (R-CHOP-21: 27, R- CHOP-14: 22) to no-RT. 96% (79/82) received RT per protocol and 5 pts in the no-RT arm received unplanned RT (4 after PR and 1 after CR/CRu). Response RT vs no-RT were CR/Cru 94% vs 84%, PR 2% vs 10%, PD 2% vs 4%. 3-year EFS was superior in pts assigned to RT (94% vs. 78%; p = 0.007), mostly due to events caused by initiation of RT (n = 5) in the no-RT arm. In an as treated analysis the difference between the RT and the no-RT arm was not significant (p = 0.136). Regarding PFS and OS no difference between the RT vs no-RT arm was detected (PFS: 95% (95% CI: 90-100) vs 90% (95% CI: 81-98), p = 0.253; OS: 98% (95% CI: 94-100) vs 96% (95% CI: 90-100), p = 0.636). Dose- densification of R-CHOP-21 by R-CHOP-14 did not improve EFS, PFS nor OS. Only 4 pts died. Conclusions: To our knowledge, this is the largest series of PMBCLs so far, which have been treated in a prospective, randomized trial in the rituximab era. The results reveal no differences between R-CHOP- 14 vs R-CHOP-21. Pts assigned to RT had a superior EFS mostly due to a higher PR rate in the no-RT arm triggering RT, with no differences in PFS and OS. The results suggest a benefit of RT only for pts, who are responding to R-CHOP with PR. Testing RT in PET-positive residual tumors in a randomized trial can solve the question, while RT in PET-negative pts is studied in the ongoing randomized IELSG 37 trial. Our results indicate a very favorable 3-year OS of 96% in PMBCL pts treated with R-CHOP. Supported by Deutsche Krebshilfe, Amgen and Roche. Clinical trial information: NCT00278408. Research Sponsor: Deutsche Krebshilfe (German Cancer Aid), Pharmaceutical/Biotech Company.

8042 Poster Session (Board #375), Fri, 8:00 AM-11:00 AM

Myeloablative versus non-myeloablative consolidative chemotherapy for newly diagnosed primary central nervous system lymphoma: Results of induction therapy in Alliance 51101.

Tracy Batchelor, Sharmila Giri, Amy S. Ruppert, Nancy L. Bartlett, Eric D. Hsi, Bruce D. Cheson, Lakshmi Nayak, John Paul Leonard, James L. Rubenstein; Brigham and Women’s Hospital, Boston, MA; Mayo Clinic, Rochester, MN; The Ohio State University, Department of Internal Medicine, Columbus, OH; Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO; Cleveland Clinic, Cleveland, OH; Georgetown University Hospital, Washington, DC; Dana-Farber Cancer Institute, Boston, MA; Meyer Cancer Center, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY; University of California, San Francisco, San Francisco, CA

Background: Optimal consolidative therapy for primary central nervous system lymphoma (PCNSL) is not defined. Avoidance of whole brain radiation may reduce risk of neurotoxicity. Non-radiation consolidative options include myeloablative chemotherapy followed by autologous stem cell transplantation (HDT/ASCT) or non-myeloablative chemotherapy. Methods: This is a randomized phase 2, National Clinical Trials Network study of induction methotrexate (MTX) (8 g/m2days 1, 15), temozo- lomide (TMZ) (150-200 mg/m2 D7-11), and rituximab (RTX) (C1 D3, 10, 17, 24 and C2 D3, 10) in four 28-day cycles followed by one cycle of cytarabine (ARA-C) (2 g/m2 BID, D1, 2) (MTRA). Following induction, patients (pts) received consolidation with thiotepa (5 mg/kg BID, D -5, -4) plus carmustine (400 mg/m2, day -6) and ASCT (Arm A) or one cycle of ARA-C (2 g/m2 BID, D1-4) plus infusional etoposide (40 mg/kg over 96h) (Arm B). The primary endpoint was median progression-free survival (PFS), designed to compare consolidation regimens. This report describes the results of the 5 cycles of induction therapy. Results: 113 pts (median age 61 years, range 33-75) were randomized (Arm A: 57, Arm B: 56) across 27 centers. 108 eligible pts who received induction therapy were evaluated. 36 pts (33.3%) did not proceed to consolidation, mainly due to disease progression (17), pt withdrawal (8), or adverse events including death (6). Grade 3 or 4 febrile neutropenia occurred in 12 pts (11.1%) during induction. Dose modifications of MTX were required in 75% of pts and 63.3% of cycles, mainly due to renal adjustments. Dose delays of MTX were required in 52.8% of pts and 22.2% of cycles. Overall response rate (CR, CRu, PR) at the end of induction was 65.7% (95% CI, 56%, 74.6%). Conclusions: While MTRA is feasible and active a significant proportion of pts did not receive consolidation, supporting the need to develop more effective induction strategies. Clinical trial information: NCT01511562. Research Sponsor: U.S. National Institutes of Health.

8043 Poster Session (Board #376), Fri, 8:00 AM-11:00 AM

Outcomes of Burkitt lymphoma (BL) managed in academic (Acad) or community (Comm) centers: real-world evidence (RWE) from 30 US sites.

Adam J. Olszewski, Izidore S. Lossos, Andrzej Stadnik, Stephen Douglas Smith, Deepa Jagadeesh, Seo-Hyun Kim, Tycel Jovelle Phillips, Seema Naik, Tatyana Feldman, Nishitha Reddy, Suchitra Sundaram, Seth Maliske, Vaishalee Padgaonkar Kenkre, Narendranath Epperla, Malvi Savani, Craig Portell, Neil Palmisiano, Andreas Kirschmer Klein, Andrew M. Evens, Burkitt Lymphoma RWE Cohort Investigators; Rhode Island Hospital-The Warren Alpert Medical School of Brown University, Providence, RI; Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, FL; Oregon Health & Science University, Portland, OR; University of Washington/Fred Hutchinson Cancer Research Center, Seattle, WA; Cleveland Clinic Taussig Cancer Institute and Case Comprehensive Cancer Center, Cleveland, OH; Rush University, Chicago, IL; University of Michigan, Ann Arbor, MI; Penn State Cancer Institute, Hershey, PA; John Theurer Cancer Center, Hackensack, NJ; Vanderbilt University Medical Center, Nashville, TN; Roswell Park Comprehensive Cancer Center, Buffalo, NY; Aspirus Wausau Hospital Regional Cancer Center, Wausau, WI; University of Wisconsin, Madison, WI; The Ohio State University, Columbus, OH; University of Minnesota, Minneapolis, MN; University of Virginia, Charlottesville, VA; Thomas Jefferson University Hospital, Philadelphia, PA; Tufts Medical Center, Boston, MA; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ

Background: Prior analyses have suggested better overall survival (OS) of cancer patients (pts) treated in Acad rather than Comm hospitals, but these disparities may reflect different patient characteristics. We examined outcomes of pts with BL in a large RWE cohort from 30 US healthcare systems (Evens, ASH 2019) with a mix of Acad and affiliated Comm sites. Methods: We collected clinical data on adults with BL diagnosed in 2009-2018, individually assigned to Acad or Comm principal setting of care. We compared duration of chemotherapy (CTx, incl. standard CODOX-M/IVAC, hCVAD/MA, DA-EPOCH), rates of complete response (CR), progression-free survival (PFS), and OS adjusting for age, sex, HIV, performance status (PS), stage, LDH . 3x upper limit of normal (ULN), involvement of bone marrow or cerebrospinal fluid (CSF), reporting adjusted risk (RR) or hazard ratio (HR) with 95% CI. Results: Among 641 BL pts, 77 (12%) were managed in Comm setting. Comm pts had lower median age (45 vs 48 in Acad, P= .049), less frequent HIV (13% vs 23%, P= .039), less marrow (21% vs 36%, P= .009) or detected CSF involvement (8% vs 15%, P= .11), and less LDH . 3xULN (21% vs 41%, P= .013), with no significant differences in sex, PS, stage, hemoglobin, or receipt of CTx (97% vs 99%). Acad sites more often applied standard intensive CTx regimens (93% vs 85%, P= .03) and rituximab (92% vs 79%, P= .001), without significant difference in median time to CTx (P= .69) or treatment-related mortality (TRM, P= .16). Pts managed in Comm (vs Acad) sites were less likely to achieve CR (61% vs 75%, P= .03; RR = 0.79 [0.65-0.95]) and had worse 3-year PFS (46% vs 67%, log-rank P= .003; HR = 2.17 [1.51-3.14]) and OS (53% vs 72%, P= .006; HR = 2.20 [1.48-3.25]). There was no significant interaction with age, sex, HIV, PS, or CSF involvement. Excess mortality concentrated in the 1st year of follow-up. CR, PFS, and OS appeared similar between Acad and Comm settings for pts receiving hCVAD or DA-EPOCH, but outcomes were significantly worse in Comm setting for pts receiving CODOX-M/IVAC. Median number of cycles did not differ between Comm or Acad sites, but median duration of CODOX-M/ IVAC delivery was significantly longer in Comm setting (113 vs 101 days, P= .023). Conclusions: In this large RWE analysis, superior outcomes of adults with BL in Acad setting were not explained by baseline patient characteristics or TRM. Differences in the use of standard CTx regimens, rituximab, duration of Ctx, and CR rates suggest need for further research on potential barriers to delivery of intensive CTx for BL in a broader Comm setting. Research Sponsor: None.

8044 Poster Session (Board #377), Fri, 8:00 AM-11:00 AM

Efficacy and safety of ABP 798 compared with rituximab: Results from the comparative clinical study in patients with non-Hodgkin’s.

Dietger Niederwieser, Caroline M. Hamm, Patrick Cobb, Mindy Mo, Cecily Forsyth, Alessandra Tucci, Vladimir Hanes, Vincent Delwail, Roman Hajek, David Chien; University of Leipzig, Leipzig, Germany; Schulich School of Medicine, West Windsor, ON, Canada; SCL Health - St Vincent Frontier, Billings, MT; Amgen Inc., Thousand Oaks, CA; Gosford Hospital, New South Wales, Australia; Spedali Civili Brescia, Brescia, Italy; Centre Hospitalier Universitaire de Poitiers, Poiters, France; Department of Hemato-oncology, University Hospital Ostrava, University of Ostrava, Ostrava, Czech Republic

Background: ABP 798* is being developed as a biosimilar to rituximab, a CD20-directed cytolytic antibody. A randomized, double-blind, active-controlled study compared the efficacy, safety, and immunogenicity of ABP 798 with rituximab reference product (RP) in subjects with CD20-positive NHL; results of the final analysis are presented here. Methods: Adult subjects with grade 1, 2, or 3a follicular B-cell NHL and low tumor burden were randomized to receive intravenous ABP 798 or RP (375 mg/m2) once weekly for 4 weeks, then at weeks 12 and 20. The primary endpoint was risk difference (RD) of overall response rate (ORR) by week 28. Secondary endpoints included RD of ORR at week 12, pharmacokinetics, pharmacodynamics, safety, and immunogenicity. Results: 254/256 randomized subjects were treated with at least one infusion of ABP 798 (n = 128) or RP (n = 126); ORR by week 28, based on independent central blinded assessment of the modified full analysis set, was comparable between the ABP 798 and RP groups (78% vs. 70%, respectively). The 2-sided 90% confidence interval of RD of ORR (-1.4%; 16.8%) was within the pre-specified margin (-15%; 35.5%) thereby establishing clinical equivalence between ABP 798 and RP. This result was supported by analyses of the secondary efficacy endpoint of RD of ORR at week 12. In the two groups, the geometric least squares means for serum concentrations over time (e.g., week 12, pre-dose: ABP 798, 21.89 vs. RP, 20.57; week 12 post-dose: ABP 798, 201.30 vs. RP, 203.52) and the extent of B-cell depletion from day 1 to day 8 (ABP 798, 98.3% vs. RP, 98.3%) were similar. Frequency, type, and severity of adverse events (AEs) were comparable between ABP 798 and RP groups; grade $3 AEs were reported in 10.9% and 10.3% of subjects and serious AEs in 3.9% and 4.0%, respectively. Most common AEs were headache, fatigue, and nausea; the most common AE of interest was infusion reactions. No new or unexpected safety signals were observed. Binding and neutralizing anti-drug antibodies were comparable between groups. Conclusions: Results of this study demonstrated clinical similarity between ABP 798 and rituximab RP in subjects with CD20-positive NHL. *At the time of this submission, ABP 798 had not been approved by the FDA or any relevant regulatory agency and the indications are yet undetermined. Please consult ABP 798’s later approved label in the relevant country for information regarding the approved uses for ABP 798. Research Sponsor: Amgen.

8045 Poster Session (Board #378), Fri, 8:00 AM-11:00 AM

Treatment stratification in B-cell PTLD after solid organ transplantation (SOT) by international prognostic index (IPI) and response to rituximab: Interim results from the PTLD-2 trial.

Ralf Ulrich Trappe, Christian Koenecke, Martin H. Dreyling, Christiane Pott, Ulrich Duehrsen, Norbert Meidenbauer, Dennis Hahn, Michael Heuser, Christian Schmidt, Matthias Ritgen, Reiner Siebert, Ilske Oschlies, Ioannis Anagnostopoulos, Heiner Zimmermann, DPTLDSG and GLA; Department of Hematology and Oncology, DIAKO Ev. Diakonie-Krankenhaus, Bremen, Germany; Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany; Department of Medicine III, University Hospital Grosshadern/LMU, Munich, Germany; Department of Internal Medicine II: Hematology and Oncology, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany; Department of Hematology, Essen University Hospital, University of Duisburg-Essen, Essen, Germany; Department of Medicine 5, University of Erlangen-Nuremberg, Erlangen, Bayern, Germany; Department of Hematology, Oncology and Palliative Care, Katharinenhospital, Stuttgart, Germany; Institute of Human Genetics, Ulm University and Ulm University Medical Center, Ulm, Germany; Department of Hematopathology, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany; Department of Pathology, University of Wurzburg, ¨ W¨urzburg, Germany

Background: The PTLD-1 trials have established risk-stratified sequential treatment of B-cell PTLD. After rituximab induction, patients (pts) in complete remission (25 %) received rituximab consolidation, while all others received R-CHOP. The PTLD-2 trial tests modified risk-stratification including clinical risk factors. These are the results of the 2nd scheduled interim analysis (40/60 planned pts). Methods: The prospective, multicenter phase II PTLD-2 trial (NCT02042391) enrols treatment-na¨ıve adult SOT recipients with CD20-positive PTLD. Key exclusion criteria are CNS involvement, ECOG . 2, pregnancy, and severe organ dysfunction or severe, active infection. Treatment consists of rituximab (1400 mg SC; first application 375 mg/m2 IV) on days 1, 8, 15 and 22. After restaging, pts in CR as well as those in PR with # 2 IPI risk factors at diagnosis (low-risk group) continue with four three-weekly courses of rituximab. Most other pts (high-risk group) receive 4 cycles of R-CHOP-21, while thoracic SOT recipients who progress under rituximab (very-high-risk group) receive six cycles of alternating R-CHOP-21 and R-DHAOx. The primary endpoint (event-free survival in the low-risk group) is not analyzed here. Secondary endpoints presented here are response and overall response (ORR) by computed tomography, overall survival (OS), time to progression (TTP) and treatment-related mortality (TRM) overall and by risk group. Results: 40 pts were recruited at 12 centers (2015 – 2019). 21/40 were kidney, 11 lung, 4 liver, 3 heart, and 1 liver/kidney transplant recipients. Median age was 54 years. 38/ 40 PTLD were monomorphic and 15/40 EBV-associated. 38 pts were evaluated for response at interim staging: 13 were allocated to the low-risk, 17 to the high-risk and 8 to the very-high-risk group. ORR was 28/30 (93 %, CR: 16/30 [53 %]). With a median follow-up of 1.9 years, the 1-year/3-year Kaplan-Meier (KM) estimates of TTP and OS in the intention-to-treat population (40 pts) were 85 %/80 % and 70 %/70 %, respectively. In the low-risk group, the 2-year KM estimate of OS was 100 %. The frequency of infections (all grades) was 50 %, and TRM occurred in 3/40 pts (8 %). Conclusions: One third of enrolled pts were treated in the low-risk group and the recruitment goal for evaluation of the primary endpoint will likely be reached. Interim efficacy and toxicity data with rituximab SC and modified risk- stratification are encouraging despite the inclusion of 35 % thoracic SOT recipients. Clinical trial information: NCT02042391. Research Sponsor: Roche.

8046 Poster Session (Board #379), Fri, 8:00 AM-11:00 AM

MAGNIFY phase IIIb interim analysis of induction R2 followed by maintenance in relapsed/ refractory indolent NHL.

David Jacob Andorsky, Morton Coleman, Abdulraheem Yacoub, Jason M. Melear, Suzanne R. Fanning, Kathryn S. Kolibaba, Frederick Lansigan, Chris Reynolds, Grzegorz S. Nowakowski, Mecide Gharibo, Jung Ryun Ahn, Ju Li, Mathias J. Rummel, Jeff P. Sharman, on behalf of the MAGNIFY Trial Investigators; Rocky Mountain Cancer Centers/The US Oncology Network, Boulder, CO; Clinical Research Alliance Inc., Weill Cornell Medicine, New York, NY; University of Kansas Cancer Center, Westwood, KS; Texas Oncology-Austin, US Oncology Research, Austin, TX; Prisma Health, US Oncology Research, Greenville, SC; Compass Oncology, US Oncology Research, Vancouver, WA; Dartmouth-Hitchcock Medical Center, Lebanon, NH; IHA Hematology Oncology Consultants–Ann Arbor, Ypsilanti, MI; Mayo Clinic, Rochester, MN; Bristol-Myers Squibb, Summit, NJ; Justus-Liebig Universitat, ¨ Giessen, Germany; Willamette Valley Cancer Institute and US Oncology Research Center, Eugene, OR

Background: Patients (pts) with relapsed iNHL have limited standard treatment options. The immunomodulatory agent lenalidomide shows enhanced activity with rituximab (ie, R2), which recently reported 39.4-mo median PFS in R/R iNHL pts (AUGMENT; J Clin Oncol. 2019;37:1188). Methods: MAGNIFY is a multicenter, phase IIIb trial in pts with R/R FL gr1-3a, MZL, or MCL (NCT01996865) exploring optimal lenalidomide duration. Lenalidomide 20 mg/d, d1-21/28 + rituximab 375 mg/m2/wk c1 and then q8wk c3+ (R2) are given for 12c followed by 1:1 randomization in pts with SD, PR, or CR to R2 vs rituximab maintenance for 18 mo. Data presented here focus on induction R2 in efficacy- evaluable FL and MZL pts (MCL not included) receiving $ 1 treatment with baseline/post-baseline assessments to analyze the primary end point of ORR by 1999 IWG criteria. Results: As of June 16, 2019, 393 pts (81% FL gr1-3a; 19% MZL) were enrolled with a median follow up of 23.7 mo (range, 0.6-57.8) for censored pts (n = 335). Median age was 66 y (range, 35-91), 83% had stage III/IV disease, with a median of 2 prior therapies (95% prior rituximab-containing). ORR was 69% with 40% CR/CRu (Table). Median DOR was 39.0 mo, and median PFS was 40.1 mo. 199 pts (51%) have completed 12c of R2, and 188 (48%) have been randomized and entered maintenance. 139 pts (35%) prematurely discontinued both lenalidomide and rituximab, primarily due to AEs (n = 52, 13%) or PD (n = 45, 11%). Most common all-grade AEs were 48% fatigue, 43% neutropenia, 36% diarrhea, 31% nausea, and 30% constipation. Grade 3/4 AE neutropenia was 36% (9 pts [2%] had febrile neutropenia); all other grade 3/4 AEs occurred in , 7% of pts. Conclusions: R2 is active with a tolerable safety profile in pts with R/R FL and MZL, including rituximab-refractory, double-refractory, and early relapse pts. Clinical trial information: NCT01996865. Research Sponsor: Bristol-Myers Squibb, Summit, NJ.

Efficacy for induction R2 in R/R iNHL. DOR, median PFS, median ORR, % CR/CRu, % (95% CI), mo (95% CI), mo* Overall 69 40 39.0 (36.8-NR) 40.1 (37.6-NR) Histology FL 70 41 NR (36.8-NR) 39.4 (30.0-NR) MZL 63 38 38.6 (29.4-NR) 41.2 (38.4-NR) R-refractory Yes 60 36 35.8 (35.2-NR) 25.9 (18.1-41.6) No 73 43 NR (38.4-NR) 41.2 (39.4-NR) Double refractory Yes† 50 26 20.1 (14.6-NR) 17.7 (10.7-23.0) No 73 44 39.0 (38.4-NR) 41.6 (39.4-NR) Early relapse Yes‡ 66 31 35.8 (22.4-NR) 26.5 (18.1-41.6) No 70 45 NR (38.4-NR) 41.2 (39.4-NR) *If pts in maintenance at cutoff, response assessments also contributed to PFS †Refractory to both rituximab (monotherapy or combo) and alkylating agent ‡Progressed or relapsed # 2 y of initial diagnosis after 1L systemic treatment

8047 Poster Session (Board #380), Fri, 8:00 AM-11:00 AM

Machine learning prediction of survival in diffuse large B-cell lymphoma based on gene-expression profiling.

Selin Merdan, Kritika Subramanian, Turgay Ayer, Jean Louise Koff, Andres Chang, Johan Van Weyenbergh, Christopher Flowers; Value Analytics Labs, Alpharetta, GA; Department of Internal Medicine Icahn School of Medicine at Mount Sinai, New York, NY; H. Milton Stewart School of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, GA; Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA; Department of Clinical and Epidemiological Virology, Rega Institute for Medical Research, Leuven, Belgium; Emory University, Winship Cancer Institute, Atlanta, GA

Background: The current clinical risk stratification of Diffuse Large B-cell Lymphoma (DLBCL) relies on the International Prognostic Index (IPI) comprising a limited number of clinical variables but is imperfect in the identification of high-risk disease. Our study aimed to: (1) develop a risk prediction model based on the genetic and clinical features; and (2) evaluate the model’s biological implications in association with the estimated profiles of immune infiltration. Methods: Gene-expression profiling was performed on 718 patients with DLBCL for which RNA sequencing data and clinical covariates were available by Reddy et al (2017). Unsupervised and supervised machine learning methods were used to discover and identify the best set of survival-associated gene signatures for prediction. A multivariate model of survival from these signatures was constructed in the training set and validated in an independent test set. The compositions of the tumor-infiltrating immune cells were enumerated using CIBERSORT for deconvolution analysis. Results: A four gene-signature-based score was developed that separated patients into high- and low-risk groups with a significant difference in survival in the training, validation and complete cohorts (p , 0.001), independently of the IPI. The combination of the gene-expression-based score with the IPI improved the discrimination on the validation and complete sets. The area-under-the-curve at 2 and 5 years increased from 0.71 and 0.69 to 0.75 and 0.74 in the validation set, respectively. Conclusions: By analyzing the gene-expression data with a systematic approach, we developed and validated a risk prediction model that outperforms existing risk assessment methods. Our study, which integrated the profiles of immune infiltration with prognostic prediction, unraveled important associations that have the potential to identify patients who could benefit from the various therapeutic interventions, as well as highlighting possible targets for new drugs. Research Sponsor: None.

8048 Poster Session (Board #381), Fri, 8:00 AM-11:00 AM

Immunohistochemical characterization of anaplastic large cell lymphoma using tissue microarray.

Poorvi Kirit Desai, Ling Zhang, Qianxing Mo, Lubomir Sokol; University of South Florida, Tampa, FL; H. Lee Moffitt Cancer Canter and Research Institute, Tampa, FL; H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL

Background: Anaplastic Large Cell Lymphoma (ALCL) is a subtype of mature T-cell lymphoma comprised of systemic (ALK+ or ALK-) and primary cutaneous (PCALCL) forms. ALK+, usually associated with NPM1-ALK gene, has a favorable prognosis. PCALCL is usually indolent. Despite worse prognosis for ALK-, pts with DUSP22 rearrangement have favorable outcomes similar to ALK+ while those with p63 aberration have poor outcomes. We hypothesize that other genetic alterations in ALCL could aid in diagnosis and prognosis. We compared protein expression levels of selected signaling molecules (JAK1, STAT3, DUSP22, ERBB4/HER4, PRDM1/BLIMP1 and SOCS3) among the subtypes and correlated to outcomes. Methods: Of 50 pts with ALCL at Moffitt (MCC) from 2000-2019, 27 tissue samples (6 ALK+, 10 ALK-, 8 PCALCL, 3 controls) met eligibility criteria. Tissue microarrays (TMAs) were constructed from formalin-fixed, paraffin-embedded lymph node biopsies. Up to 3 replicate cores were taken from each block. Immunohistochemistry was performed with antibodies to the selected proteins. Stained TMA slides were scanned using the Aperio™ ScanScope XT2 to determine % positive biomarker stain within each core per established algorithm. Statistics: ANOVA was used to compared protein expression levels, with pairwise tests when significant. T-test compared PCALCL to systemic ALCL. Boxplots were created for differences in protein expression levels and time to event outcomes (OS and RFS) using Log rank test and Cox proportional hazards models. Kaplan-Meier curves were used for clinical time-to-event outcomes and quartiles of the protein expression levels. Results: The 3 subgroups had a significant difference in SOCS3 expression with mean and std respectively: 42.4% (0.153), 17.4% (0.089), and 21.0% (0.155), p = 0.008. Among all pairs, ALK+ and PCALCL groups were statistically different (P = 0.011). Patients with high BLIMP1 ($28.5%) across 3 ALCL subgroups were associated with better median OS (not reached) in comparison to pts with lower expression (27.3 mos) (Log rank test p = 0.014, HR = 0.17, 95% CI 0.034-0.829). The same was seen for median RFS (81.1 vs. 12.5 mos). (Log rank test p = 0.009, HR 0.23, 95% CI 0.069-0.755). Conclusions: High BLIMP1 suggests favorable prognosis in ALCL and could potentially be a positive prognostic marker. High SOCS3 appears more prevalent in PCALCL than systemic and could aid in differential. Larger samples should be used to validate results. Secondary markers like Bcl-2 can be considered in the future to correlate expression levels to targeted treatments like venetoclax. Research Sponsor: Uni- versity of South Florida Graduate Medical Education Grant ($7500).

8049 Poster Session (Board #382), Fri, 8:00 AM-11:00 AM

The Integration of PD1 blockade with epigenetic therapy is highly active and safe in heavily treated patients with T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL).

Enrica Marchi, Helen Ma, Francesca Montanari, Ahmed Sawas, Jennifer K Lue, Changchun Deng, Kareema T Whitfield, Sandra Klein, Luigi Scotto, Salvia Sanjay Jain, John Lister, Nora N Benanni, Mark A Francescone, Wonseog S Kim, Pier Luigi Zinzani, Owen A. O’Connor; Center for Lymphoid Malignancies, Columbia University Medical Center, New York, NY; Columbia University Medical Center, New York, NY; Center for Lymphoid Malignancies, New York, NY; Center for Lymphoid Malignancies, Department of Medicine, Columbia University Medical Center, New York, NY; Beth Israel Deaconess Medical Center, Newton, MA; Division of Hematology and Cellular Therapy, Allegheny Health Network, Pittsburgh, PA; Mayo Clinic, Rochester, MN; Department of Radiology, Columbia University Medical Center, New York, NY; Samsung Medical Center, Seoul, South Korea; Institute of Hematology Seragnoli, ` University of Bologna, Bologna, Italy

Background: Our group has demonstrated that combinations of epigenetic modifiers produce potent synergy in pre-clinical models of PTCL and induce the expression of cancer testis antigen, suggesting a role in the addition of the immune-checkpoint inhibitor, pembrolizumab. Methods: This is a phase 1b study of pembrolizumab combined with pralatrexate alone (Arm A), with pralatrexate + decitabine (Arm B), or decitabine alone (Arm C) in patients with relapsed and refractory PTCL and CTCL. A standard 3+3 dose-escalation is applied in the triplet Arm (Arm B) while in the doublet Arms (A and C) de-escalation is applied in case of toxicity. Pharmacokinetic and pharmacodynamic studies are ongoing. Results: We treated a total of 12 patients with 4 patients in each Arm. All patients that received at least one dose of drug were evaluable for toxicity. There was a dose limiting toxicity (DLT) in each arm including prolonged grade 3 thrombocytopenia (Arm A), febrile neutropenia (Arm B), grade 3 hyponatremia, and rash (Arm C). There were no treatment-related deaths. Six patients out of 12 were evaluable for response at the time of this analysis. One patient achieved a complete remission, 2 had partial remission, 1 had stable disease, and 2 experienced progression of disease. Interestingly, all of the responses were seen in the triple combination of pralatrexate, decitabine, and pembrolizumab. Table summarizes the patient characteristics, toxicities, and response rates. Conclusions: These preliminary clinical data suggest that the integration of pembrolizumab on an epigenetic backbone is safe and demonstrates encouraging responses in patient with PTCL and CTCL. Clinical trial information: 03240211. Research Sponsor: Merck.

Patient characteristics, toxicities and responses (n = 12). Median age, years (range) 65 (38 - 77) Sex Male 6 Female 6 Race White/Non-Hispanic 6 White/Hispanic 1 Black 3 Asian 2 Histology PTCL, NOS 5 AITL 3 Mycosis Fungoides 2 ATLL 1 Sezary Syndrome 1 Stage at diagnosis I 1 II 1 III 4 IV 5 Tumor Stage 1 Median number of prior therapies (range) 2 (1-5) Adverse Event, Grade 3/4, n (%) Thrombocytopenia 1 Neutropenia 2 Fatigue 1 Vomiting 1 Hyponatremia 1 Rash 1 Evaluable/Total Patients (Best Response) Arm A 2/4 (POD, POD) Arm B 2/4 (CR, PR) Arm C 1/4 (SD)

8050 Poster Session (Board #383), Fri, 8:00 AM-11:00 AM

Sintilimab for relapsed/refractory (r/r) extranodal NK/T cell lymphoma (ENKTL): Extended follow-up on the multicenter, single-arm phase II trail (ORIENT-4).

Jianyong Li, Rong Tao, Lei Fan, Yongping Song, Yu Hu, Wei Zhang, Yafei Wang, Linxinyu Xu, Xing Sun, Hui Zhou; Jiangsu Province Hospital, Nanjing, China; Department of Hematology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China; Union Hospital Tongji Medical College Huazhong Universtiy of Science and Technology, Wuhan, China; Peking Union Medical College Hospital, Beijing, China; Tianjin Medical University Cancer Institute and Hospital, Tianjing, China; Innovent Biologics, Inc., Suzhou, China; Innovent Biologics, Inc., Shanghai, China

Background: Patients with r/r ENKTL have a poor prognosis after failing an asparaginase-based regimen. The overexpression of PD-L1 induced by EBV infection is a potential mechanism for ENKTL to avert immune surveillance. Sintilimab, a fully human anti-PD-1 monoclonal antibody, has demonstrated efficacy in r/r ENKTL after the primary analysis of the ORIENT-4 study. Here, we report the updated efficacy and safety results with extended follow-up. Methods: Patients with pathologically confirmed r/r ENKTL were enrolled. Sintilimab was given 200 mg IV Q3W, until PD, death, unacceptable toxicity, or withdrawal from the study. Treatment beyond PD is allowed. Tumor response evaluation was performed by both PET-CT and CT/MRI with contrast. The primary endpoint was objective response rate per Lugano 2014. Data cut-off date for this analysis was Jan 17, 2020. Results: A total of 28 patient were enrolled and treated. With a median follow-up of 26.9 months (range, 23.3 to 28.6), the median treatment duration was 24.15 months (range, 1.4 to 28.7). Of 20 patients with progressive disease (PD) by investigator per Lugano 2014 criteria, 19/20 (95%) patients received treatment beyond PD. The median OS has not been reached and 24-month OS rate was 78.6% (95% CI, 58.4% to 89.8%). ORR was 67.9% (95% CI, 47.6% to 84.1%), including 4 pts who experienced PD prior to having a response. DCR was 85.7%, including 5 pts who experienced PD before SD or response. Median duration of response was 4.1 months (range, 1.9 to 15.2+). After treatment, the mean EQ-5D-5L VAS Score (from 79.3 to 90.8), EQ-5D-5L Index Value (from 0.8 to 0.9) and EORTC QLQ-C30 (from 70.5 to 87.3) were all increased. The Treatment-related adverse events (TRAEs) of any grade occurred in 28 (100%) pts; grade 3 occurred in 11 (39.4%) pts, most commonly, decreased lymphocyte count (2 [7.1%]) and diabetes (2 [7.1%]); no grade 4-5 TRAE. Conclusions: In addition to an encourage response, sintilimab also demonstrated long-term clinical benefit, with 78.6% of 24-month OS rate, and favorable long-term safety profile after extended follow-up. Considering the high rate (95%) of treatment beyond PD, Lugano 2014 may not be a suitable criteria for evaluating the efficacy of anti-PD- 1 antibody in r/r ENKTL. Clinical trial information: NCT03228836. Research Sponsor: Innovent Biologics, Inc.

8051 Poster Session (Board #384), Fri, 8:00 AM-11:00 AM

Three-year follow-up of treatment-na¨ıve and previously treated patients with Waldenstr¨om macroglobulinemia (WM) receiving single-agent zanubrutinib.

Constantine Si Lun Tam, Stephen Opat, Paula Marlton, David Gottlieb, David Simpson, Gavin Cull, David Ritchie, Emma Verner, Javier Munoz, Alessandra Tedeschi, Jane Huang, William Novotny, Ziwen Tan, Eric Holmgren, Siminder K. Atwal, John Francis Seymour, Andrew Warwick Roberts, Judith Trotman; Peter MacCallum Cancer Centre, Melbourne, St Vincent’s Hospital, Fitzroy, University of Melbourne, Parkville and Royal Melbourne Hospital, Parkville, Victoria, Australia; Monash Health, Monash University, Clayton, Victoria, Australia; Princess Alexandra Hospital and University of Queens- land, Brisbane, Queensland, Australia; Faculty of Medicine and Health, University of Sydney, West- mead Hospital, Sydney, Australia; North Shore Hospital, Auckland, New Zealand and BeiGene USA, Inc., San Mateo, CA; Sir Charles Gairdner Hospital and University of Western Australia, Perth, WA, Australia; Peter MacCallum Cancer Centre, Melbourne, University of Melbourne, Parkville, Victoria, Australia; Concord Repatriation General Hospital and University of Sydney, Concord, Australia; Banner MD Anderson Cancer Center, Gilbert, AZ; ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; BeiGene USA, Inc., San Mateo, CA; BeiGene (Beijing) Co., Ltd., Beijing, CA, China

Background: Inhibitors of Bruton tyrosine kinase (BTK) have established therapeutic activity in patients with WM. Zanubrutinib, a potent and selective BTK inhibitor was evaluated in a phase 1/2 study in treatment-na¨ıve (TN) and relapsed/refractory (R/R) patients with WM. Methods: Patients had TN or R/R WM and required treatment as per International Workshop on WM (IWWM) criteria. Treatment consisted of oral zanubrutinib at 160 mg twice daily (n = 50) or 320 mg once daily (n = 23) until disease progression or unacceptable toxicity. Efficacy endpoints included the proportion of patients achieving a complete response (CR) or very good partial response (VGPR) in accordance with IWWM-6 criteria. Efficacy analyses were conducted on the 73 patients evaluable (24 TN, 49 R/R). Results: Between September 2014 and August 2018, 77 patients with WM (24 TN and 53 R/R) began treatment with zanubrutinib (55% aged . 65 years; 21% aged . 75 years). At a median follow up of 32.7 months, 73% remain on treatment. Reasons for treatment discontinuation included adverse events (AE) in 13% (only one related), disease progression (10.4%), and other (3.9%). Results are presented for TN and R/R combined. The overall response rate was 96% and VGPR/CR rate was 45%. The rates of VGPR/CR increased over time; 22% at 6 mos, 33% at 12 months and 45% at 24 months. Three-year progression- free survival (PFS) was 81%, and overall survival (OS) was 85%. The most commonly reported AEs were upper respiratory tract infection (52%), contusion (33%, all grade 1) and cough (22%). AEs of interest include neutropenia (18.2%), major hemorrhage (4%), atrial fibrillation/flutter (5%), and grade 3 diarrhea (3%). Conclusions: Long-term follow up with continued zanubrutinib treatment demonstrated deep and durable responses in the majority of WM patients. The rates of VGPR/CR increased with prolonged therapy. Disease progression was uncommon. The safety profile of long-term zanubrutinib therapy in these patients was tolerable. Clinical trial information: NCT02343120. Research Sponsor: BeiGene.

Efficacy and safety outcomes. TN WM (n = 24), R/R WM (n = 53), Total (n = 77), Assessment % % % VGPR/CR rate 33.3 51.0 45.2 36-mo PFS 91.5 76.2 80.5 36-mo OS 100.0 80.2 84.8 AEs leading to 12.5 13.2 13.0 discontinuation ‡Grade 3 AEs 45.8 64.2 58.4 Grade 5 AEs 0 9.4 6.5 Atrial fibrillation/ flutter 4.2 5.7 5.2 Major hemorrhage 8.3 1.9 3.9 ‡Grade 3 infections 8.3 35.9 27.3

8052 Poster Session (Board #385), Fri, 8:00 AM-11:00 AM

Prognostic relevance of CD4+ T-cells in the microenvironment of newly diagnosed follicular lymphoma (FL) patients is independent of the tumor gene expression profile.

Patrizia Mondello, Angelo Fama, Melissa C. Larson, Andew L. Feldman, Zhi-Zhang J Yang, Jose Caetano Villasboas, Sarah Huet, Bruno Tesson, Susan L. Slager, Brian K. Link, Sergei Syrbu, Anne Novak, Thomas Matthew Habermann, Thomas E. Witzig, Grzegorz S. Nowakowski, Gilles A. Salles, James Robert Cerhan, Stephen M. Ansell; Memorial Sloan Kettering Cancer Center, New York, NY; Arcispedale Santa Maria Nuova, Azienda Unit`a Sanitaria Locale-IRCCS, Reggio Emilia, Italy; Mayo Clinic, Rochester, MN; Hospices Civils de Lyon, Pierre-Benite, ´ France; Institut Carnot CALYM, Paris, France; University of Iowa Carver College of Medicine, Iowa City, IA; University of Iowa Hospitals and Clinics, Iowa City, IA; Division of Hematology, Mayo Clinic, Rochester, MN; Centre Hospitalier Lyon Sud, Pierre Benite, ´ France; Department of Health Sciences Research, Mayo Clinic, Rochester, MN

Background: A significant proportion of patients with FL experience an early relapse and a subsequent poor outcome. While several prognostic indices have been developed, none were designed to predict early failure. Recently, we established that lack of intrafollicular CD4+ T-cell expression predicted risk of early failure, and integrating this microenvironment biomarker with the Follicular Lymphoma International Prognostic Index, termed BioFLIPI, further improved identification of FL patients at risk of early failure (Blood 2019;134(suppl1):121). However, the microenvironment may be influ- enced by the genetic composition of tumor. We investigated whether the CD4 biomarker and BioFLIPI were impacted by genetic features of the tumor as assessed by a 23-gene expression prognostic score (Lancet Oncol 2018;19:549-61). Methods: Of the 186 cases with FL grade 1-3A treated with immunochemotherapy (IC) in our prior study, 152 had digital expression quantification of 23 selected genes (23-GEP score), which used RNA from formalin-fixed, paraffin-embedded samples. Event-free survival (EFS) was defined as time from diagnosis to progression, relapse, retreatment, or death. Early failure was defined as failing to achieve EFS at 24 months. Risk of early failure was estimated using odds ratios (ORs) and 95% confidence intervals from logistic regression models. We also used Cox regression to assess associations with continuous EFS and overall survival (OS). Results: 28% of patients failed to achieve EFS24. Lack of CD4+ intrafollicular expression (38% of patients, OR = 2.33, p = 0.024) and high risk 23-GEP score (26% of patients, OR = 3.52, p = 0.001) each predicted early failure, and in a multivariable model that included FLIPI, both CD4+ (OR = 2.26, p = 0.046) and 23- GEP score (OR = 2.26, p = 0.0.057) remained predictors. Similarly, BioFLIPI modeled as a continuous score (1-4, OR per one point increase = 2.31, p , 0.001) predicted early failure, and the association remained (OR = 2.14, p , 0.001) when the high risk 23-GEP score (OR = 2.79, p = 0.013) was included in the model. When stratified on 23-GEP score, BioFLIPI was a stronger predictor of early failure in low risk (74%, OR = 2.51, p = 0.002) relative to high risk (26%, OR = 1.55, p = 0.27) patients. Similar patterns were observed for EFS and OS. Conclusions: CD4+ T-cell infiltrate and tumor gene expression appear to be independently predictive of early failure in newly diagnosed FL patients treated with IC. Future studies should integrate and validate these measures. Research Sponsor: U.S. National Institutes of Health.

8053 Poster Session (Board #386), Fri, 8:00 AM-11:00 AM

Atezolizumab + obinutuzumab + venetoclax in patients with relapsed or refractory diffuse large B-cell Lymphomas (R/R DLBCL): Primary analysis of a phase II trial from LYSA.

Charles Herbaux, Olivier Casasnovas, Pierre Feugier, Gandhi Damaj, Reda Bouabdallah, Stephanie Guidez, Loic Ysebaert, Herve Tilly, Steven Le Gouill, Luc Fornecker, Nicolas Daguindau, Nadine Morineau, Corinne Haioun, Emmanuel Gyan, David Sibon, Remy ´ Gressin, Roch Houot, Gilles A. Salles, Franck Morschhauser, Guillaume Cartron; Centre Hospitalier Regional ´ Universitaire de Lille, Institute of Hematolog-Tranfusion, Lille, France; CHU Dijon, Dijon, France; Department of Hematology, CHU Nancy, Nancy, France; Department of Hematology, University Hospital, School of Medicine, Caen, France; Institut Paoli-Calmettes, Marseille, France; Poitiers University Hospital/ INSERM CIC 1402, Poitiers, France; Department of Haematology, Institut Universitaire du Cancer de Toulouse— Oncopole,ˆ Toulouse, France; Department of Hematology, Centre Henri Becquerel, University of Rouen, Rouen, France; CHU Nantes and UMR892 INSERM, Nantes, France; University Hospital of Strasbourg, Strasbourg, France; Hematologie ´ clinique CH Annecy Genevois, Annecy, France; CHD Vendee, ´ Hematology, La Roche-sur-Yon, France; Henri Mondor University Hospital, University Hospital, Creteil, ´ France; CHU de Tours-Hopitalˆ Bretonneau, Tours Cedex, France; Hopitalˆ Necker-Enfants Malades Hematology, Paris, France; Universite ´ Grenoble Alpes, Institut Albert Bon- niot, Departement d’H´ematologie Clinique, Centre Hospitalier et Universitaire de Grenoble-Alpes, Grenoble, France; Centre Hospitalier Universitaire Pontchaillou, Rennes, France; Centre Hospitalier Lyon Sud, Pierre Benite, ´ France; CHU Lille-Hopital Claude Huriez, Lille, France; CHU de Montpellier, Montpellier, France

Background: R/R DLBCL treatment remains challenging. Atezolizumab (ATE) and obinutuzumab (OBI) are monoclonal antibodies acting respectively to inhibit T-lymphocyte exhaustion or by inducing lymphoma cells cytotoxicity, whereas venetoclax (VEN) is a small molecule inhibiting BCL-2. Com- bining tumor-targeted therapies with agents that enhance anti-tumor immunity represents an attractive treatment paradigm. This LYSA sponsored multicenter phase 2 trial (NCT03276468) evaluate the combination of ATE, OBI and VEN in R/R B lymphomas, we present here primary efficacy and safety data fromthe DLBCL cohort. Methods: Patients $18 years with biopsy-confirmed R/R DLBCL who failed at least one line of therapy were eligible. OBI was given IV at the dose of 1 g on day (D) 1, 8 and 15 of cycle (C) 1 and on D1 from C2 to C8 every 3 weeks. ATE was given IV, 1.2 g every 3 weeks, started at D2 of C1, then administered at D2 of each cycle for 24 cycles. VEN was given orally at 800 mg/D at full dose, started on D8C1 for 24 cycles. The primary endpoint wasthe Overall Metabolic Response Rate (OMRR) by Lugano criteria at the end of induction (EOI) after 8 cycles of ATE, OBI and VEN (M6) or at premature treatment discontinuation. Results: At the time of the primary analysis (03 Jan 2020), 58 pts were enrolled and the median follow-up was 9 months [6.9-11.8]. Baseline characteristics were: median age, 70 years; male, 53.4%; Ann Arbor Stage IV, 84.5%; aaIPI ($2), 63.2%; . 2 prior lines of therapy, 83.6%; and refractory to last line of prior regimen, 63.6%. The OMRR at EOI was measured at 23.6% [14.58%-34.93%], including 18% of CMR. To date, these responses seem durable with only 3 reported relapses. According to the highest diameter mass, OMRR was 38.5% versus 10.3%, , 5cm and . 5cm respectively; P = 0,02. All three treatments were stopped in 78% of patients, mostly for progressive disease. At the time of analysis, a median of 4 cycles [1-8] has been administered. A total of 48 (84.2%) pts experienced grade 3–4 adverse event (AE) and 6 (10.5%) had an AE that led to discontinuation of any drug.AE of grade 3 or more reported in at least 20% of patients were neutropenia (33.3%) and lymphopenia (35.1%). Of note, a grade 3 autoimmune colitis and a grade 1 hypothy- roidism were reported during induction. Conclusions: The ATE, OBI and VEN combinationappears to be well tolerated. The OMRR rate at EOI is comparable with currently available treatment options in this population, with durable responses. The OMRR seems better in patients with a low tumor burden. Clinical trial information: NCT03276468. Research Sponsor: Roche and AbbVie.

8054 Poster Session (Board #387), Fri, 8:00 AM-11:00 AM

Identification of predicted neoantigen vaccine candidates in follicular lymphoma patients.

Cody Ramirez, Felix Frenkel, Olga Plotnikova, Vladislav Belousov, Alexander Bagaev, Elena Ocheredko, Susanna Kiwala, Jasreet Hundal, Zach L Skidmore, Marcus Watkins, Michelle Becker-Hapak, Catrina Fronick, Robert Fulton, Robert Schreiber, Nancy L. Bartlett, Brad S. Kahl, Ravshan Ataullakhanov, Malachi Griffith, Obi Griffith, Todd A. Fehniger; McDonnell Genome Institute, Washington University School of Medicine in St. Louis,St.Louis,MO;BostonGene,LLC,Waltham,MA;Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO; Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO

Background: Follicular lymphoma (FL) is incurable with conventional therapies and poorly responsive to immune checkpoint blockade. There is a need for new therapies without long-term complications of chemotherapy and with curative potential. We hypothesize that FL contains tumor-specific mutant antigens (TSMAs) that can be targeted by the immune system by vaccination. Recent reports have highlighted the potential for unique immunoglobulin peptides to elicit immune response in lymphomas. We utilized whole exome sequencing (WES) and RNA sequencing (RNA-Seq) of FL patient samples to infer HLA genotype, and predict TSMAs with the goal of designing a personalized cancer vaccine, supported by recent reports of this approach in solid cancers. Methods: DNA and RNA from 58 patients’ FL biopsies underwent WES and RNA-Seq. pVACtools and MiXCR predicted potential somatic and B-cell clonotype neoantigens, which were filtered to identify high quality TSMAs. B-cell oligo- clonality was determined by comparison to B-cell receptor (BCR) repertoire profiling of healthy individual lymph nodes. RNA-seq data allowed us to identify expressed TSMAs. Complementary in silico analysis based on mRNA-based peptide reconstruction and custom HLA affinity binding pre- dictions were performed. Results: An average of 52 somatic mutations per patient (range: 2-172) were identified. At least one high quality TSMA was predicted for 57 of 58 patients. Five or more TSMA candidates were identified for 52 (90%) patients with a mean of 17 predicted peptides per patient (range: 0-45). 81% (813/1,004) of the total predicted TSMA peptides arose from missense mutations, 9% (94/1,004) from indels, and 10% (97/1,004) from BCR. 78% (45/58) of patients have both somatic and BCR vaccine candidates, while 21% (12/58) of patients had only somatic vaccine candidates. Predicted TSMAs were identified in multiple genes recurrently mutated in lymphoma (e.g., BCL2). There was a high prediction concordance with the orthogonal BostonGene Vaccine Module V1 pipeline. These pre-clinical results led to a first-in-human pilot trial of personalized TSMA vaccine combined with anti-PD-1 mAb for rel/ref FL patients (NCT03121677), with one response observed within 4 patients evaluable for response to date. Conclusions: TSMA peptides suitable for cancer vaccines were identified for most FL patients via next-generation sequencing, MiXCR and pVACtools. This pre-clinical study suggests that FL patients will be candidates for TSMA vaccine clinical trials and pilot clinical results provide proof of concept for this approach. Research Sponsor: Siteman Cancer Center, Other Foundation, The Jamie Erin Follicular Lymphoma Research Consortium.

8055 Poster Session (Board #388), Fri, 8:00 AM-11:00 AM

Multi-omics analysis of mantle cell lymphoma reveals an immune-cold tumor microenvironment associated with ibrutinib resistance.

Krystle Nomie, Preetesh Jain, Nikita Kotlov, Vitaly Segodin, Qingsong Cai, Yang Liu, Lucy Navsaria, Viktor Svekolkin, Alexander Bagaev, Felix Frenkel, Ravshan Ataullakhanov, Nathan Hale Fowler, Michael Wang; The University of Texas MD Anderson Cancer Center, Department of Lymphoma/ Myeloma, Houston, TX; BostonGene, LLC, Waltham, MA; BostonGene, Inc, Waltham, MA; The University of Texas MD Anderson Cancer Center, Houston, TX

Background: Mantle cell lymphoma (MCL) is an aggressive and incurable B-cell lymphoma. Although the role of the MCL tumor microenvironment (TME) in survival and therapeutic response has been studied, greater knowledge regarding the tumor-immune interaction is needed to develop MCL immunotherapeutic strategies. Methods: Whole exome sequencing (WES; n = 41) and RNA-seq (n = 93) were performed on fresh peripheral blood, apheresis, or biopsy MCL patient primary samples. Joint WES and RNA-seq mutation calling, expression analysis were performed by BostonGene. Results: Both tumor and TME molecular signatures were characterized based on ibrutinib response. Concurrent analysis of MCL biopsy samples with an additional previously published cohort (n = 122; Scott et al., JCO, 2017) identified 4 MCL microenvironment signatures (Nomie et al., Blood, 2019) in which the ibrutinib-resistant MCL samples primarily belonged to the “stroma-enriched” subtype (29%; 6/8 resistant, non-immune with increased stromal signature and tumor-promoting cytokines), whereas most of the ibrutinib-sensitive samples were assigned to the “immune-hot” subtype (53%, 9/9 sensitive; anti-tumor infiltration, high immune and checkpoint molecule expression with low stromal expression, Chi-square test p-value = 0.001). NOTCH1 gain-of-function mutations (25%, 3/12 resistant) in the PEST domain were found exclusively in the ibrutinib-resistant cohort associated with the microenvironment-depleted subtype. Frequent recurring inactivating mutations in the epigenetic modifier KMT2D (30%) were identified in MCL cells associated with the ‘immune-suppressed” subtype (p , 0.05). Loss-of-function mutations in epigenetic modifiers have been tied to immune evasion. PD-L1 was significantly downregulated in the ibrutinib-resistant MCL tumors (p = 0.03), indicating that targeting the PD-L1 and PD-1 immune checkpoint axis may not be beneficial. Conclusions: Ibrutinib sensitivity and resistance were defined by immune-hot and immune-cold TME portraits, respectively, suggesting that the TME has a prominent role in mediating ibrutinib response. Ibrutinib has been suggested to activate the immune TME through its off target inhibition of interleukin 2–inducible T-cell kinase (ITK). The immune activation by ibrutinib suggests that anti-tumor activity of ibrutinib may be better harnessed by combining ibrutinib with immunotherapy. Research Sponsor: None.

8056 Poster Session (Board #389), Fri, 8:00 AM-11:00 AM

Phase Ib trial combining rapid determination of drug-drug interaction (DDI) followed by a dose finding period to assess safety and preliminary efficacy of fimepinostat plus venetoclax in patients with aggressive B-cell lymphoma.

Tycel Jovelle Phillips, Sven De Vos, Jason Westin, Stefan K. Barta, Jonathon Brett Cohen, Krish Patel, Sonali M. Smith, John M. Pagel, Vikram Kansra, Dena Grayson, Anas Younes, Connie Lee Batlevi; University of Michigan, Ann Arbor, MI; Ronald Reagan University of California Los Angeles Medical Center, Santa Monica, CA; The University of Texas MD Anderson Cancer Center, Department of Lymphoma/Myeloma, Houston, TX; University of Pennsylvania, Philadelphia, PA; Emory University Winship Cancer Institute, Atlanta, GA; Swedish Cancer Institute, Seattle, WA; The University of Chicago, Chicago, IL; Curis, Inc., Lexington, MA; Curis, Lexington, MA; Memorial Sloan Kettering Cancer Center, New York, NY

Background: Fimepinostat (F), a dual inhibitor of PI3K (a, b, d) and HDACs type 1/2, causes suppression of MYC levels (Shulman et al., 2017). A pooled analysis of diffuse large B-cell lymphoma (DLBCL) pts treated with F in two Ph 1/2 trials revealed an objective response rate in evaluable/ITT MYC-altered DLBCL pts of 29%/23%, respectively (Landsburg et al., 2018). Based on compelling preclinical activity of F in combination with venetoclax (V) (a Bcl2 inhibitor), we initiated a Ph 1b/2 study of F + V in pts with relapsed or refractory (R/R) DLBCL or high-grade B-cell lymphoma (HGBL), with or without MYC alteration. V is metabolized primarily by CYP3A, and preclinical studies showed that F may inhibit CYP3A4 (IC50 of 13.58 and 0.28 mM for midazolam and testosterone, respectively), suggesting F could cause DDI with V. Methods: Cohorts of patients received increasing dose levels of F administered on a 5-days-on/2-days-off (5/2) schedule in combination with daily V in 21-day cycles (Cohort 1: F 30 mg QD 5/2 + V 400 mg QD; Cohort 2: F 60 mg QD, 5/2 + V 400 mg QD; Cohort 3: F 60 mg QD 5/2 + V 800 mg QD). A potential DDI was assessed during Cycle 0 (Table), where PK for V (10 mg) monotherapy was compared to that for V (10 mg) in the presence of F. Patient PK samples were collected, analyzed and reviewed in , 10 days to determine the final ramp-up dose level of V. Results: As of 1-Feb-2020, 16 pts have been enrolled in 2 dose cohorts. Intensive PK analysis of 13 pts showed only mild (# 2-fold) to no increase in V exposure in the presence of F. In Cohort 1 (n = 6), the mean AUC increased 1.6-fold, and mean Cmax by 1.5-fold. In Cohort 2 (n = 7), no increase in mean AUC (0.9-fold) or Cmax (1.0-fold) was observed. Accordingly, all pts ramped up V to 100% of the target dose (400 mg) upon entering Cycle 1; rapid escalation of V was well tolerated. DLT was observed in 1 pt (Grade 3 diarrhea) in Cohort 2. Overall, 75% of TEAEs have been mild or moderate (Grade 1/2), and most were of limited duration. 11 pts (69%) experienced SAEs; 4 pts (25%) had SAEs considered related to either F or V. Conclusions: Real-time PK evaluation showed that F had only a mild to no DDI with V. F + V is well tolerated at clinically active dose levels, and evaluation of higher dose-level cohorts was ongoing. Enrollment in Cohort 2 remains on-going. Clinical trial information: NCT01742988. Research Spon- sor: Curis, Inc.

Cycle Cycle Cycle: 0 1 Day: 12-6- 89-11- 15 16 17 18 19 - End of PK Eval- 1-2 5 7 10 14 uation Period V (dose 10 10 10 20 50 100 (100- Continue to target 200- mg): 200) dose 400 F: XX X X X X X X X PK: XX XX XXX X X

8057 Poster Session (Board #390), Fri, 8:00 AM-11:00 AM

Haemophagocytic lymphohistiocytosis (HLH) in patients with large B-cell lymphoma treated with standard of care (SOC) axicabtagene ciloleucel (Axi-cel).

Sairah Ahmed, fateeha furqan, Paolo Strati, Jason Westin, Luis Fayad, Frederick B. Hagemeister, Hun Ju Lee, Swaminathan Padmanabhan Iyer, Ranjit Nair, Loretta J. Nastoupil, Simrit Parmar, Maria Alma Rodriguez, Felipe Samaniego, Raphael Steiner, Michael Wang, Chelsea Camille Pinnix, Christopher Flowers, Sandra B. Horowitz, Misha Hawkins, Sattva Swarup Neelapu; The University of Texas MD Anderson Cancer Center, Department of Lymphoma/Myeloma, Houston, TX; Rochester General Hospital, Rochester, NY; The University of Texas MD Anderson Cancer Center, Houston, TX; MD Anderson Cancer Center/University of Texas, Houston, TX; The University of Texas MD Anderson Cancer Center, Department of Radiation Oncology, Houston, TX; University of Texas MD Anderson Cancer Center, Houston, TX; MD Anderson Cancer Center, Houston, TX

Background: HLH is a rare but serious complication of chimeric antigen receptor (CAR) T cell therapy, characterized by severe immune activation, and immune mediated multi-organ failure. Diagnosis is difficult in the context of cytokine release syndrome (CRS) and optimal treatment and outcomes are unclear. Methods: Retrospective, descriptive analysis of patients with relapsed/refractory LBCL treated with SOC axi-cel at MD Anderson Cancer Center between 01/2018 - 10/2019 (data cut-off 12/21/ 2019). Progression-free survival (PFS) defined as time from axi-cel infusion to progression/death or last follow-up. Diagnosis of HLH per HLH-2004 and CART cell therapy toxicity guidelines (Neelapu, 2018) Results: One hundred and five patients with relapsed/refractory LBCL included, 6 diagnosed with HLH. No significant difference in baseline characteristics, disease stage, international prognostic index or inflammatory markers at baseline between groups, with exception of platelet count which was lower in HLH group 116 [37-129] versus 141 [9-391] (p = 0.07). Development of HLH was early after CART cell infusion at a median 11 days [7 – 78 days] with 3 patients having bone marrow hemophagocytosis; all 6 had abnormalities in liver function tests, fibrinogen, triglycerides, and at least 1 ferritin level . 10,000. CART toxicity in HLH cohort: 4 patients experienced grade 0-1 CRS, and 1 with grade 2 CRS while 3 HLH patients experienced grade 3-4 IEC-associated neurotoxicity syndrome (ICANS), and 2 patients had grade 0-1 ICANS. Five HLH patients treated with high dose steroids, and tocilizumab; anakinra administered in 2 patients. Four of 6 patients had resolution of HLH with treatment and didn’t require escalation to HLH specific therapy however 1 patient was treated with steroids/etoposide. PFS and overall survival (OS) were significantly shorter in HLH group, PFS 1 months vs 8 months, respectively (p , 0.001) and median OS 2 months vs not reached, respectively (p = 0.001) follow up 10 months (95% CI 8-12 months). One patient died of acute respiratory failure, 2 patients died of HLH and multi-organ failure without progressive disease (PD). Of 3 remaining patients, all had radiographic PD at day 30, 2 of whom died of PD. Conclusions: HLH is likely an underreported complication of CART cell therapy, and patients with HLH have significantly worse outcomes. In this series the majority of patients died of PD, not the syndrome itself. More information is necessary to design treatment strategies that won’t compromise CART outcomes. Research Sponsor: None.

8058 Poster Session (Board #391), Fri, 8:00 AM-11:00 AM

Safety and efficacy of TQ-B3525, a novel and selective oral PI3K a/d inhibitor, in Chinese patients with advanced malignancies: A phase I dose-escalation and expansion trial.

Huaqing Wang, Wenqi Jiang, Su Li, Yu Wang, Peng Sun, Pei Zhou, Yang Zheng, Jing Zhan, Zhiming Li; First People’s Hospital of Tianjin, Tianjin, China; State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China; Sun Yat-sen University Cancer Center, Guangz- hou, China; Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China; People’s Hospital of Tianjin, Tianjing, China; Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, China; Sun Yat-Sen University Cancer Center, Guangzhou, China

Background: TQ-B3525 is a novel and selective oral PI3K a/d inhibitor with activity 41 and 138 folds higher than Buparlisib against PI3K a and PI3K d in pre-clinical research. This Phase I study (NCT03510767) assessed the safety, tolerability, pharmacokinetics and antitumor activity of TQ- B3525 in Chinese patients with advanced malignancies. Methods: Patients with relapsed or refractory (R/R) lymphoma who have experienced at least two prior systemic anti-cancer treatments, and advanced solid tumor who have failed standard anti-cancer treatment, were enrolled. TQ-B3525 was administered orally from 2mg, 5mg, 10mg, 20mg once daily (qd) to 10mg, 20mg twice daily (bid). DLT was observed in the first cycle (28 days) of dose-escalation phase. Dose-expansion phase started at the dose level which objective response occurs. Results: Between June 2018 and December 2019, a total of 40 patients were enrolled, Including 27 patients with R/R lymphoma and 13 patients with advanced solid tumor. Three DLTs (both grade 3 hyperglycemia) were observed: two in the 20mg bid dose cohort and one in the 10mg bid. The common AEs of all grades were hyperglycemia (65.0%), glycosylated hemoglobin increased (35.0%) and diarrhea (32.5%). Grade 3 or 4 treatment-related AEs occurred in 11 patients (27.5%), with the most common one also being hyperglycemia (10.0%). TQ- B3525 was rapidly absorbed (Tmax: 1-2 h) and moderately eliminated (T1/2: 10-12 h). At steady state, the geometric mean AUC0-24 and Ctrough of TQ-B3525 at 20mg qd were 1060.7 6 198.6 h*ng/mL and 23.4 6 9.5 ng/mL, which was above IC50 (4.2 ng/ml). 23 lymphoma patients were evaluable for clinical response per 2014 Lugano Classification. The overall response rate (ORR) was 60.9% (95% CI, 38.5- 80.2). The ORR at $10mg qd was 70.0% (14/20, [95% CI, 49.9-90.1]). For R/R FL, the ORR was 72.7% (8/11, [95% CI, 46.4-99.1]). At data cut-off (2nd February, 2020), the median PFS for lymphoma was not reached (events rate: 33.3%). The longest duration of response at data cutoff was 11.8 months in a patient with FL. Conclusions: TQ-B3525 is well-tolerated in Chinese patients with advanced malignancies, and demonstrated high promising antitumor activity in R/R lymphoma patients. Recommended phase II dose was established at 20mg qd. A single-arm phase 2 trial of TQ- B3525 in patients with R/R FL is currently underway. Clinical trial information: NCT03510767. Research Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

8059 Poster Session (Board #392), Fri, 8:00 AM-11:00 AM

The BCR repertoire comparison, lymphoma typing model and OS predicted model in 5 different pathological lymphomas: T-LBL/ALL, PTCL-NOS, B-MCL, B-FL, and DLBCL.

Wenhua Jiang, Shiyong Zhou, Jian Li, Mingyou Gao, Kuo Zhao, Limeng Zhang, Xiaojing Xie, Ning Zhao, Caijuan Tian, Zanmei Xu, Zhenzhen Zhang, Fang Yan, Yi Pan, Pengfei Liu; Second Hospital of Tianjin Medical University, Tianjin, China; Tianjin Medical University Cancer Institute and Hospital, Tianjin, China; Tianjin University Hospital, Tianjin, China; Tianjin Marvel Medical Laboratory, Tianjin Marvelbio Technology Co., Ltd, Tianjin, China; Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, China

Background: Lymphatic system cancer is characterized by high heterogeneity in histology and clinical manifestations, B-cell antigen receptor (BCR) plays a vital role in anti-tumor immune responses. This study aimed to compare the BCR repertoire and identify some specific immune markers for different pathological lymphomas. Methods: 5 pathological types of non-Hodgkin’s lymphoma (T-LBL/ALL, PTCL-NOS, B-MCL, B-FL, DLBCL) were collected, with reactive lymph node (RLN) hyperplasia as control. All patients were tested by high-throughput immunohistochemical sequencing (HTS-IR) to analyze the correlation between B-cell immunohistochemistry and clinical indicators, and constructed new strategy typing and overall survival (OS) predicted models for lymphomas. Results: The BCR repertoire had the highest diversity in RLN, followed by T-LBL/ALL, PTCL-NOS, DLBCL, B-MCL and B-FL. The diversity of BCR repertoire and similarity of B cell antigens were higher in B-MCL and B-FL patients. Similar to RLN, T-LBL/ALL and PTCL-NOS had broad and diverse V-J pairs, and rare in B-MCL, B-FL and DLBCL. RLN patients were with the highest average number of amino acids, followed by T-LBL/ALL, DLBCL, PTCL-NOS, B-MCL and B-FL. The expressed amino acid sequencing of ARDLIALDY, ARRPGSFDY, ARDIAGWGAVAGLLGRAYYGMDV, and ARDGPYGGNSVEYFQH were markedly different among 5 groups. Patients tended to recurrence expressed ASLDSSPSGFC, ARGMTTVTTAPNY, ARVPLYDDQNINDV and AGGVGGYDWGSYYFDY (P = 0.01605, 0.02869, and 0.01569), and prone to metastasis with expressions of ARVKEFYGILTGYDY, AHSIIGSSWYNWFDP and VRDGGWQSNNWLGFDV (P = 0.04259, 0.0450 and 0.0481). For all patients, 18 (7 negative, 11 positive) and 12 (10 negative, 2 positive) IGH V-J pairs were respectively associated with lymphoma recurrence and metastasis. The top 3 most significant pairs were IGHV7-4-1_IGHJ4, IGHV3-53_IGHJ5 and IGHV3-7_IGHJ5 bound up with recurrence (P = 0.0019, 0.0020 and 0.0021), and IGHV3- 74_IGHJ1, IGHV1-69_IGHJ3 and IGHV1-2_IGHJ1 related to metastasis (P = 0.0022, 0.010 and 0.019). The accuracy of typing model in training and test sets was 78.125% (25/32) and 60% (6/10), respectively. The OS model can predict long ($ 24 months) or short ( , 24 months) OS. Conclusions: Our study identified new biomarkers, constructed novel lymphoma typing model and OS predicted model based on B cell repertoire. It provides a comprehensive understanding of immune response, and contributes to the diagnosis and prognosis of non-Hodgkin’s lymphoma. Research Sponsor: National Natural Science Foundation of China.

8060 Poster Session (Board #393), Fri, 8:00 AM-11:00 AM

REFLECT real-world evidence (RWE) prospective study update: Efficacy and safety results of Sandoz biosimilar rituximab (SDZ-RTX) for the treatment of diffuse large B-cell lymphoma (DLBCL).

Manfred Welslau, Norbert Walter Marschner, Burkhard Joerg Otremba, Julian Topaly, Larissa Bittencourt da Silva; Onkologische Schwerpunktpraxis am Klinikum, Onkologie Aschaffenburg, Aschaffenburg, Germany; Medical Practice for Oncology and Hematology, Freiburg, Germany; Onko- logische Praxis, Oldenburg-Delmenhorst, Oldenburg, Germany; MVZ Klinikum Osnabruck ¨ GmbH, Osnabruck, ¨ Germany; Sandoz Group, a Novartis Division, Holzkirchen, Germany

Background: SDZ-RTX (Rixathon) is approved in more than 20 countries and regions, including highly regulated markets e.g. Europe, Japan and Switzerland for all labeled indications of reference rituximab. REFLECT is the first prospective post-approval study to evaluate a rituximab biosimilar as a curative therapy in untreated pts with CD20+ DLBCL. This interim analysis adds up efficacy and additional safety results on the previously presented data (Welslau et al, ASCO and EHA 2019). Methods: Adult patients (pts) were treated with SDZ-RTX and cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) according to the product label. The primary endpoint is to evaluate the effectiveness of Rixathon measured by complete response (CR) rate at the end of treatment. Secondary endpoints are overall response rate (ORR), progression-free survival at 24 months and adverse events (AEs). Data were collected at baseline and all scheduled treatment and follow-up visits, which is still ongoing. No imputation was made for missing values, and endpoints are summarized descriptively. Results: As of Sep 30, 2019, 170 pts were enrolled, and R-CHOP treatment was close to completion. The median age of pts was 70 years, and 52% were women. Overall, 38% of pts completed the first 12-month observation period, 41% were ongoing, while 21% of pts discontinued. Most of the pts (~80%) had an ECOG score of 0 (35%) or 1 (46%). Early staging (I–II2), low to intermediate disease risk (IPI 0-2), and known B symptoms were reported for 55%, 50%, and 30% of pts, respectively. CR rate at the end of treatment was 57% (defined as the revised response criteria for malignant lymphoma by Cheson et al, 2007 that excludes complete remission/unconfirmed [CRu]). Summary of efficacy is reported in the Table. Overall, 83% of pts experienced AEs, the most common being anemia (23%), fatigue (21%), and polyneuropathy (15%). Treatment-related AEs were reported for 28% of pts. Rates of any serious AEs (SAEs) and treatment-related SAEs were 37% and 6.5%, respectively. On-treatment deaths and all deaths were reported in 2.4% and 4.7% of pts, respectively. Conclusions: REFLECT is the first prospective post-approval study to evaluate a rituximab biosimilar as a curative therapy in untreated pts with DLBCL. This interim analysis results re-confirms the expected safety and efficacy profile for DLBCL patients treated with R-CHOP. Research Sponsor: Sandoz Group, a Novartis Division.

Summary of response. Response (%) All patients (N = 170) ORR 88% CR 57% PR 31% Not available 3% Missing 9%

8061 Poster Session (Board #394), Fri, 8:00 AM-11:00 AM

Clinicopathologic features and outcomes of de novo transformed indolent lymphoma.

Collin K Chin, Chan Cheah, Preetesh Jain, Nathan Hale Fowler, Luis Fayad, Jason Westin, Maria Alma Rodriguez, Mansoor Noorani, Sattva Swarup Neelapu, Fredrick B. Hagemeister, L Jeffrey Medeiros, Francisco Vega, Felipe Samaniego, Christopher Flowers, Loretta J. Nastoupil; The University of Texas MD Anderson Cancer Center, Department of Lymphoma/Myeloma, Houston, TX; Sir Charles Gairdner Hospital, Nedlands, Australia; University of Texas MD Anderson Cancer Center, Houston, TX

Background: Untreated transformed indolent lymphoma (unTIL) can present as a composite lymphoma (COM), 2 or more separate sites of disease with one site transformed (discordant; DIS) or following indolent lymphoma sequentially (SEQ). Current practices are guided by small retrospective studies or extrapolated from trials involving non-transformed lymphomas. Methods: 353 patients (pts) with biopsy-proven unTIL treated with curative chemoimmunotherapy between 01/2000 to 01/2019 were included (intention to treat). All indolent B-cell lymphomas (iNHL) were included except CLL/SLL. Patients with MCL and non-DLBCL transformation were excluded. Prior therapy for iNHL was not allowed except one line of non-chemotherapy-based therapy. Kaplan-Meier method was used for time- to-event analysis including progression-free (PFS) and overall survival (OS). Results: 252 (71%) pts presented with COM, 50 (14%) DIS and 51 (14%) SEQ lymphoma. The underlying iNHL was: 308 (87%) follicular lymphoma, 37 (10%) nodal MZL, 7 (2%) MALT lymphoma, and 1 (0.3%) WM. Frontline therapy (FLT) included: RCHOP for 271 (77%), DAEPOCHR for 60 (17%), clinical trial for 7 (2%), BR for 4 (1%), RHCVAD for 2 (1%), RCEOP for 2 (1%), radiation therapy for 2 (1%), RFND for (1%) 2, RCVP for 2 (1%), and rituximab only for 1 (0.3%). 9 (3%) pts had ASCT in first remission. 50 (15%) pts received maintenance rituximab (MR) with fewer cases of HGBL-DH compared to the non- MR cohort (0% v 10%). With a median follow-up of 3.4 years (range 0.1-19.1), 4-year PFS and OS rates were 59% and 88%. By univariate analysis (UVA) the underlying type of iNHL, cell-of-origin and choice of induction therapy (DAEPOCHR v RCHOP) were not associated with inferior outcomes. SEQ transformations were associated with inferior OS on UVA (P = 0.02) which was not significant on multivariable analysis (MVA) (P = 0.3). MVA identified ECOG PS . 1, B symptoms and HGBL-DH as independent prognostic factors for inferior PFS and OS. In patients who achieved PR or greater following FLT, MR was associated with improved PFS on MVA (HR 0.6, 95% CI 0.3-0.9, P = 0.04) without an OS benefit (P = 0.2). 39 (31%) pts relapsed with iNHL only (mPFS 2.4 yrs, 4-yr OS 94%) and 88 (69%) relapsed with transformed lymphoma (mPFS 1.1 yrs, 4-yr OS 69%) with no significant difference in pattern of relapse with MR (P = 0.2). Conclusions: The clinicopathologic features of unTIL are similar to those of de novo DLBCL. Escalation of therapy beyond R-CHOP may not be required in the absence of HGBL-DH. unTIL should be included in future clinical trials involving de novo DLBCL given the similar clinicopathologic features. Research Sponsor: None.

8062 Poster Session (Board #395), Fri, 8:00 AM-11:00 AM

Alternative anti-CD20 antibody versus desensitization for lymphoma patients with drug hypersensitivity reactions requiring discontinuation of rituximab, obinutuzumab, or ofatumumab.

Paola Ghione, Erel Joffe, Nadia De Paola, Timothy Mainardi, Sarah J. Noor, Sabela Bobillo, Patricia L. Myskowski, M. Lia Palomba, Alison J. Moskowitz, Anthony R. Mato, Fushen Sha, Gottfried Von Keudell, David J. Straus, Ariela Noy, Anas Younes, Paul A. Hamlin, Renier J. Brentjens, Miguel Angel Tejedor-Alonso, Steven M. Horwitz, Andrew David Zelenetz; Memorial Sloan Kettering Cancer Center, New York, NY; Allergy and Immunology, New York Presbyterian Hospital, New York, NY; Vall d’Hebron University Hospital, Barcelona, Spain; Center for CLL, Memorial Sloan Kettering Cancer Center, New York, NY; Memorial Sloan Kettering Cancer Center, New Haven, CT; Hospital Universitario Fundacion Alcorcόn, Madrid, Spain

Background: Immunotherapy with anti CD20 is often associated with mild easily manageable infusion reactions. In rare cases, patients experience severe drug hypersensitivity reactions (DHR) serum sickness or anaphylaxis. These in turn may lead to discontinuation of the drug. In our experience, switching to a different anti-CD20 agent is a feasible alternative to discontinuation or desensitization protocols. Methods: From our pharmacology database we identified all the patients that received rituximab and/or obinutuzumab, and/or ofatumumab, and/or all the patients who received a flat dose of less than 50 mL of the same drugs and were followed at our institution. From the medical record, we identified all the cases where the anti-CD20 antibody was changed due to allergy, serum sickness or other types of DHR, and all those who received minimal doses of anti-CD20 in the context of a desensitization protocol. DHRs were evaluated either by an allergist, or by retrospective review following the World Allergy Organization guidelines. Our primary comparison, was to assess the proportion of pts able to completed planned infusion of abs using either approach (Fisher’s exact Test). Results: Among 343 patients receiving at least two different anti-CD20 antibodies or a flat dose of , 50 mL, we identified 44 patients experiencing severe DHRs needing intervention. At the time of the reaction, 16 (36%) received the anti-CD20 as single agent, 24 (54%) in combination with chemotherapy, 4 (9%) in combination with ibrutinib or lenalidomide. In 9 (20%) patients the reaction was defined as anaphy- lactoid (8 rituximab; 1 obinutuzumab) and in 8 (18%) patients, all receiving rituximab, as serum sickness. Episodes of DHR were addressed with either desensitization (n = 29) or change of anti-CD20 agent (n = 25), 9 patients received both of these approaches, one patient switched anti-CD20 antibodies twice. Overall, 21 desensitizations were successful (72.4%), 8 failed; 23 changes of anti-CD20 were successful (92%) and 2 failed (p = 0.09). Conclusions: In patients with DHR use of an alternative anti-CD20 antibody is safe and is an alternative or complementary approach to anti-CD20 desensitization. Research Sponsor: None.

8063 Poster Session (Board #396), Fri, 8:00 AM-11:00 AM

CNS involvement by North American-ATLL (NA-ATLL) is associated with discrete patterns and molecular profile involving XPO1 E571 and KLF2/PI3KCD in selected cases.

Nishi Shah, Riya Jayesh Patel, Astha Thakkar, Shafia Rahman, Ana Acuna-Villaorduna, Urvi Shah, Diego Adrianzen Herrera, Shira Slasky, Kira Gritsman, Mendel Goldfinger, Noah Saul Kornblum, Aditi Shastri, Ioannis Mantzaris, Lizamarie Bachier-Rodriguez, Ira Braunschweig, Amit Verma, Katharine Anne McNeill, B. Hilda Ye, Murali Janakiram, R. Alejandro Sica, BMT/PA Group; Montefiore Einstein Center for Cancer Care, Bronx, NY; Jacobi Medical Center, Bronx, NY; Montefiore Medical Center, Bronx, NY; Cleveland Clinic Foundation, Cleveland, OH; Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY; Memorial Sloan Kettering Center, New York, NY; Larner College of Medicine, University of Vermount, Burlington, VT; Albert Einstein College of Medicine, Bronx, NY; Rutgers Univ- Robert Wood Johnson Medcl Ctr, Edison, NJ; Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY; Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Division of Hematology, Oncology and Transplantation, University of Minne- sota, Minneapolis, MN; Stanford University, Palo Alto, CA

Background: Information on central nervous system (CNS) involvement with NA-ATLL is limited. In this study, we describe CNS involvement in ATLL patients at a tertiary hospital in New York City. Methods: We considered CNS involvement if one of the following criteria was met 1) cerebrospinal fluid (CSF) cytology or flow cytometry was positive 2) CNS imaging was positive for disease involvement or 3) Physical exam findings were compatible with neurologic involvement. Results: Of 94 NA-ATLL patients, 21 (22.3%) had CNS involvement by ATLL. CSF was involved in 13/21 and 5/21 patients at diagnosis and relapse respectively. At diagnosis, MRI showed CNS involvement in brain and spine in 5/21 (24%) and 3/ 21 (14%) cases respectively. At relapse, imaging revealed brain and spine involvement in 2 patients each. Neurological exam was abnormal in 7 (33%) and 3 (14%) cases at diagnosis and relapse respectively. Next generation exon targeted sequencing was performed in 9 cases. Table shows the mutations (mtn) and functional groups with frequencies. XPO1 E571K mutation was present in 2 patients with extensive CNS disease and refractory to conventional treatment with an overall survival (OS) of 2 months. To our knowledge, this is the first time that XPO1 E571K is reported in a T-Cell malignancy. We also describe here a second set of mutations with CNS involvement (KLF2 and PI3KCD) in 2 patients. Median OS was 8.5 months, Median RFS was 6.5 months in our series. In most cases, the lymphomatous phenotype appeared to have direct mass-like extension (5/21) with several cases of accompanying osteolytic spine or skull lesions, whereas cases with hematogenous involvement tends to spread to the CSF by traversing the brain blood barrier. Conclusions: In this report we describe patterns of CNS involvement in ATLL and the associated mtns. We also describe two unique cases of XPO1E571K mtn in a TCL. Research Sponsor: None.

List of mtns in CNS-ATLL pts grouped by predominant pathway. Cell cycle and DNA maintenance ATM 2 CDKN2A 2 CDKN2B 1 TP53 1 SETBP1 1 Class I MHC protein complex B2M 1 Epigenetic and histone modification ARID1A 1 HIST1H1E 1 EP300 1 SMARCB1 1 G-coupled receptor P2RY8 1 JAK/STAT JAK3 1 NFKB REL 1 NOTCH NOTCH1 3 SPEN 1 Nuclear export signal-dependent protein transport XPO1 2 Other FAS 2 CDH1 1 ZFHX4 1 NTRK1 1 PI3K/AKT/MTOR PIK3CD 2 Ras HRAS 1 NRAS 1 NF1 1 Receptor tyrosine kinases ALK 1 ERBB3 1 Splicing factor mtn SF3B1 1 Transcriptional regulation (TR) TBL1XR1 3 KLF2 3 AR 2 MYC 1 GATA2 1 GATA3 1 TCF3 1 TR of granulopoiesis CSF3R 1 Wnt-B catenin APC 2 FAT1 1 CTNNB1 1

8064 Poster Session (Board #397), Fri, 8:00 AM-11:00 AM

Safety of acalabrutinib (Acala) monotherapy in hematologic malignancies: Pooled analysis from clinical trials.

Richard R. Furman, John C. Byrd, Roger G. Owen, Susan Mary O’Brien, Jennifer R. Brown, Peter Hillmen, Deborah Marie Stephens, Priti Patel, Liat Schwartz-Sagi, Marshall Baek, Beth Christian, Martin J.S. Dyer, Matthew J. Streetly, Clare Chui Ling Sun, Simon Rule, Michael Wang, Paolo Ghia, Wojciech Jurczak, John M. Pagel, Jeff P. Sharman; Weill Cornell Medicine, New York Presbyterian Hospital, New York, NY; The Ohio State University Comprehensive Cancer Center, Columbus, OH; St. James’sUniversityHospital, Leeds, United Kingdom; Chao Family Comprehensive Cancer Center, University of California, Irvine, CA; Dana-Farber Cancer Institute, Boston, MA; University of Utah Huntsman Cancer Institute, Salt Lake City, UT; Acerta Pharma, South San Francisco, CA; The Ernest and Helen Scott Haematological Research Institute, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom; Guy’sHospital,Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom; National Heart, Lung, and Blood Institute, Bethesda, MD; Plymouth University Medical School, Plymouth, United Kingdom; The University of Texas MD Anderson Cancer Center, Houston, TX; Universita ` Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milan, Italy; Maria Sklodowska-Curie National Institute of Oncology, Krakow, Poland; Swedish Cancer Institute, Seattle, WA; Willamette Valley Cancer Institute/US Oncology, Eugene, OR

Background: Acala is a next-generation, highly selective, covalent Bruton tyrosine kinase inhibitor approved in the US for patients (pts) with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and previously treated mantle cell lymphoma (MCL). We evaluated the safety profile of acala monotherapy (monotx) in multiple B cell malignancies. Methods: Data from pts with activated B- cell diffuse large B-cell lymphoma, CLL, follicular lymphoma, MCL, multiple myeloma, prolymphocytic leukemia, Richter syndrome, SLL, or Waldenstr¨om macroglobulinemia treated with $1 dose of acala monotx in 9 studies were pooled. Acala was administered at 100 mg BID in most pts (100–400 mg total dose daily). Adverse events (AE) were assessed. Results: A total of 1040 pts were included (median age: 67 y [range: 32–90]; ECOG status #1: 93%; median exposure duration: 24.6 mo [range: 0–58.5]). A total of 360 (34%) pts discontinued acala, most commonly due to progressive disease (PD; 17%). AEs led to acala discontinuation in 97 (9%) pts; those in . 2 pts were pneumonia (n = 5) and thrombocytopenia (n = 4). Incidence of AEs, including the most common (any grade and grade $3), are shown in the Table. Events of clinical interest (ECIs) included atrial fibrillation (afib) of any grade in 46 (4%) pts and grade $3 in 13 (1%) pts; major hemorrhage (any grade) in 37 (4%) pts; grade $3 infection in 183 (18%) pts; hypertension (any grade) in 79 (8%) pts and grade $3 in 36 (4%) pts; and second primary malignancies (SPM) excluding non-melanoma skin cancer (NMSC; any grade) in 68 (7%) pts. Median (range) time to first onset in days for each ECI (any grade) was: afib, 522 (8–1280); major hemorrhage, 293 (4–1327); infections, 92 (1–1317); hypertension, 157 (2–1345); SPM excluding NMSC, 339 (7–1499). Death was reported in 139 (13%) pts, most commonly due to PD (6%) and AEs (5%). Conclusions: Acala monotx has a favorable tolerability profile with increased exposure across multiple mature B cell malignancies. Additional analyses will further explore the longitudinal characteristics of AEs. Research Sponsor: Acerta Pharma, a member of the AstraZeneca group.

Incidence of any AEs, serious AEs, and most common AEs (any grade occurring in $15% of pts and grade $3 occurring in $5% of pts). Any Grade, n (%) Grade ‡3, n (%) Any AEs 1001 (96) 563 (54) Serious AEs 405 (39) 360 (35) Common AEs Headache 393 (38) 11 (1) Diarrhea 382 (37) 27 (3) Upper respiratory tract infection 229 (22) 8 (1) Contusion 226 (22) 0 Nausea 226 (22) 12 (1) Fatigue 222 (21) 18 (2) Cough 218 (21) 1 ( , 1) Arthralgia 119 (19) 7 (1) Anemia 138 (13) 81 (8) Neutropenia 128 (12) 116 (11) Pneumonia 90 (9) 53 (5)

8065 Poster Session (Board #398), Fri, 8:00 AM-11:00 AM

A phase I/II study to assess safety and dose of ixazomib in combination with cyclophosphamide and dexamethasone in newly diagnosed patients with light chain (AL) amyloidosis.

Keren Osman; Rockefeller Univ, New York, NY

Background: AL amyloidosis is an incurable clonal plasma cell disorder characterized by tissue deposits of immunoglobulin light chain fragments leading to organ dysfunction and death. Standard treatment for newly diagnosed patients (pts) has traditionally included oral melphalan + dexamethasone as well as high-dose melphalan + ASCT. Here we report preliminary results of a Phase 1/2, open-label, multi- institution study of ixazomib (I) in combination with cyclophosphamide (Cy) and dexamethasone (D) in newly diagnosed AL amyloidosis. Methods: Eligible pts are $18 years with newly diagnosed, untreated biopsy-proven AL amyloidosis. A total of up to 30 pts will be enrolled, with up to 18 in the dose escalation arm (phase 1) and 12 in the maximum tolerated dose (MTD) expansion arm (phase 2) according to a classical 3+3 design. Four dose levels were evaluated in phase 1. I and Cy are given orally (PO) on days 1, 8, 15, and D 20mg PO on days 1, 8, 15, 22 of each 28-day cycle. Treatment continues for a total of 6 cycles or until disease progression, significant toxicity or withdrawal. The primary study objective in phase 1 is to establish the MTD and in phase 2 is to determine hematologic/organ response rate. Results: As of February 2020, 120 pts have been enrolled; 16 in phase 1 and 4 in phase 2. The MTD was established at dose level 3 (I 4mg and Cy 500mg). Median age is 65 years (range 46-79), 12 (67%) are male. Light chain isotype is lambda in 14 (78%). Seven pts (39%) have cardiac, 10 (56%) renal, 4 (22%) gastrointestinal, 1 (6%) hepatic, 2 (11%) soft tissue involvement, with 22% having multi-organ involvement. Four pts (22%) completed 6 cycles of therapy and 6 (33%) remain on study with a median of 3 cycles completed. Eight of 16 pts (50%) had at least 1 drug-related adverse event (AE) (any grade), most commonly edema (19%), fatigue (19%), dizziness/lightheadedness (13%) and lymphopenia (13%). Grade 3/4 AEs were rare with grade 3 lymphopenia, anemia, and hyponatremia occurring in 13%, 6%, and 6% of pts, respectively. Of 18 evaluable pts, 7 (39%) achieved $VGPR with the median time to best response 2 cycles (1-5). Conclusions: The combination of ICyD for pts with newly diagnosed AL amyloidosis is safe and well tolerated. Phase 1 is completed and the recommended phase 2 dose has been established. Deep hematologic responses ($VGPR) have occurred and time to response appears similar to standard of care induction regimens, ie CyBorD. Phase 2 response data will be updated at the meeting. Research Sponsor: Takeda.

TPS8066 Poster Session (Board #399), Fri, 8:00 AM-11:00 AM

Trial in progress: a phase II, multicenter, single-arm study of zanubrutinib (BGB-3111) in patients with previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma intolerant of prior treatment with ibrutinib.

Ian Flinn, Mazyar Shadman, Benjamin Bruce Freeman, Dih-Yih Chen, Xiaoping Zhang, Aileen Cohen, Sunhee K. Ro, Jane Huang, Jeff P. Sharman; Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA; Summit Medical Group, Florham Park, NJ; BeiGene USA, Inc., San Mateo, CA; Willamette Valley Cancer Institute and Research Center, Eugene, OR

Background: Ibrutinib (ibr), a Bruton tyrosine kinase inhibitor (BTKi), was shown to improve patient outcomes in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL); however, adverse events (AEs) were the most common reason for discontinuing ibr (50% and 63% of discontinuations in relapse/refractory (R/R) and frontline patients, respectively; Haematologica. 2018:103:874). Zanu- brutinib, an approved BTKi for mantle cell lymphoma, was specifically engineered to optimize selectivity. Pooled clinical data from 6 zanubrutinib monotherapy trials in B-cell malignancies (N=682 patients; R/R CLL/SLL [n=91]) suggested that zanubrutinib monotherapy was well tolerated and demonstrated a low rate of treatment discontinuation from AEs (9%; Tam, EHA 2019). Presented here is a trial-in-progress that will evaluate whether zanubrutinib monotherapy may serve as a therapeutic option for patients with CLL/SLL who have become ibr intolerant. Methods: The ongoing phase II, multicenter, US, single-arm, open-label study (NCT04116437, BGB-3111-215) will evaluate zanubrutinib monotherapy (160mg twice daily) as a treatment option for patients with CLL/SLL intolerant to prior ibr treatment. Approximately 60 patients will be enrolled from ~30 community medical centers. Key inclusion criteria include CLL/SLL requiring treatment per International Work- shop on CLL criteria (Blood. 2018;131:2745) before ibr therapy, intolerance to ibr (defined as an unacceptable AE for which, per investigator’s opinion, ibr treatment should be discontinued despite optimal supportive therapy), resolution of ibr-related AEs to grade #1 or baseline, and an ECOG PS 0-2. Key exclusion criteria include having an intervening cancer therapy between ibr and zanubrutinib, a documented disease progression during ibr treatment up to the time of enrollment, and a history of central nervous system (CNS) hemorrhage. The primary endpoint is frequency and severity of protocol- specified treatment-emergent AEs (diarrhea, myalgia, muscle spasm, arthralgia, hypertension, fatigue, rash, atrial fibrillation, and hemorrhage excluding CNS hemorrhage). The secondary endpoints include overall response rate, progression-free survival, and patient-reported outcomes. An exploratory endpoint was added to evaluate clinical effects (physical activity, treatment-related symptoms, and quality of life) using a smartphone app. Recruitment is ongoing. Clinical trial information: NCT04116437. Research Sponsor: BeiGene.

TPS8067 Poster Session (Board #400), Fri, 8:00 AM-11:00 AM

An intergroup collaboration for advanced stage classical Hodgkin lymphoma (cHL) in adolescents and young adults (AYA): SWOG S1826.

Sharon M. Castellino, Michael Leo LeBlanc, Alex Francisco Herrera, Susan K. Parsons, Angela Punnett, David C. Hodgson, Sarah C. Rutherford, Nadia Khan, Louis S. Constine, Kelly Davison, Anca A. Prica, Jonathan W. Friedberg, Kara M. Kelly; Emory University, Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta, Atlanta, GA; Southwest Oncology Group Statistical Center, Seattle, WA; City of Hope National Medical Center, Duarte, CA; Tufts Medical Center, Boston, MA; SickKids Hospital, Toronto, ON, Canada; Princess Margaret Cancer Centre, Toronto, ON, Canada; Weill Cornell Medicine, New York, NY; Fox Chase Cancer Center, Philadelphia, PA; University of Rochester Medical Center, Rochester, NY; McGill Universtiy, Montreal, ´ QC, Canada; Sunnybrook Health Science Centre/ Odette Cancer Centre, Toronto, ON, Canada; Department of Pediatric Oncology, Roswell Park Cancer Institute and Oishei Children’s Hospital, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY

Background: Treatment for pediatric cHL varies considerably from that in adult cHL. Hence there are gaps in risk prediction and optimal therapy for de-novo advanced stage disease across the adolescent and young adult (AYA) age spectrum. Early access to novel agents for AYA could be facilitated via collaboration with adult research groups through the U.S. National Cancer Institute’s National Clinical Trials Network (NCTN). The PD-1 inhibitor Nivolumab (Nivo) has safety and efficacy in relapsed and refractory disease in children and adults, but has not been evaluated in de-novo disease to date. Methods: North American cooperative group lymphoma chairs, Cancer Therapy Evaluation Program (CTEP) representatives and patient advocates met to establish consensus on the comparison arms and study design, based on recent historical approaches across adult and pediatric groups. Study cham- pions were identified across North American cooperative groups and include expertise in imaging, radiation oncology, biology and patient-reported outcomes. A therapeutic study was designed with the primary aim being to compare progression-free survival with novel targeted agents in advanced stage cHL. S1826 (NCT03907488), led by SWOG Cancer Research Network, opened to accrual in July 2019. Eligibility criteria include age . 12 years, and Stage III or IV cHL. Patients are randomized (1:1) to 6 cycles of either Nivo-Adriamycin, Vinblastine, Dacarbazine (AVD) or Brentuximab vedotin (Bv)- AVD. Enrollment is stratified by age, baseline International Prognostic Score, and provider intent to use involved site radiation therapy (ISRT). Protocol-prescribed ISRT is response-adapted, based on end of therapy imaging. The primary endpoint is a comparison of progression-free survival between arms. Secondary clinical endpoints include comparison of: overall survival, metabolic response at the end of therapy, physician-reported adverse events, patient-reported adverse events, and health-related quality of life (overall, and specific to fatigue and neuropathy). This unique intergroup collaboration demonstrates the process and the feasibility of consensus study designs toward early adoption of targeted therapies and harmonization of treatment approaches for AYA populations. Clinical trial information: NCT03907488. Research Sponsor: U.S. National Institutes of Health.

TPS8068 Poster Session (Board #401), Fri, 8:00 AM-11:00 AM

Brentuximab vedotin in combination with nivolumab, doxorubicin, and dacarbazine in newly diagnosed patients with advanced-stage Hodgkin lymphoma (Trial in Progress).

Judah D. Friedman, Hun Ju Lee, Linda Ho, Ian Flinn; University Hospitals Seidman Cancer Center, Cleveland, OH; The University of Texas MD Anderson Cancer Center, Houston, TX; Seattle Genetics, Inc., Bothell, WA; Sarah Cannon Research Institute-Tennessee Oncology, Nashville, TN

Background: Brentuximab vedotin (BV, ADCETRIS) is approved for the treatment of adults with treatment-na¨ıve Stage III or IV cHL in combination with AVD (Connors 2017). Nivolumab is approved for treatment of adults with relapsed/refractory cHL. Both agents have been well tolerated with promising activity when combined with multi-agent chemotherapy. The combination of BV plus nivolumab was evaluated as a frontline treatment option for patients (pts) with cHL who are over 60 years and ineligible for or declined conventional combination chemotherapy (Friedberg, 2018). The ongoing study reported an ORR of 82% in 11 pts and appears well tolerated in this population. In another trial in 93 patients in the first salvage setting, the combination produced a 67% CR rate (Herrera 2018, Moskowitz 2019) and the majority of patients were able to undergo subsequent stem cell transplant. It is reasonable to expect that the combination of BV, nivolumab, A, and D (AN + AD) will result in high response rates and be well tolerated, with potentially less toxicity. Methods: SGN35-027 (NCT03646123) is a phase 2 study designed to evaluate the efficacy and safety of A+AVD when administered with growth factor prophylaxis in pts with stage III/IV cHL (Part A). Part B will evaluate the combination of AN + AD in a similar patient population. The primary objective of Part B is to estimate the CR rate at EOT in pts with treatment-na¨ıve advanced cHL. Patients in Part B will have Ann Arbor Stage IIB/III/IV cHL or Stage IIA cHL with bulky mediastinal disease. Enrollment is ongoing in both parts of the study. Approximately 50 pts will be enrolled in Part B. All pts will be treated with BV 1.2 mg/ kg, nivolumab 240 mg, doxorubicin 25 mg/m2, and dacarbazine 375 mg/m2, administered separately by IV infusion on Days 1 and 15 of each 28-day cycle for up to 6 cycles. Efficacy will be assessed by PET/ CT scans at C2 and EOT. Disease assessments will be performed periodically during follow up. Disease response and progression will be assessed using Lugano with the incorporation of LYRIC (Cheson 2016). Clinical trial information: NCT03646123. Research Sponsor: Seattle Genetics, Inc.

TPS8069 Poster Session (Board #402), Fri, 8:00 AM-11:00 AM

Frontline brentuximab vedotin in Hodgkin lymphoma and CD30-expressing peripheral T- cell lymphoma for older patients and those with comorbidities.

Christopher A. Yasenchak, Rodolfo Eduardo Bordoni, Victor Y. Yazbeck, Dipti Patel-Donnelly, Tim Larson, Robert Brownell Sims, Matthew Genyeh Mei; Willamette Valley Cancer Institute and Research Center/US Oncology Research, Eugene, OR; Georgia Cancer Specialists, Marietta, GA; Massey Cancer Center, Richmond, VA; FNVHO, Fairfax, VA; Minnesota Oncology/The US Oncology Network, Minneapolis, MN; Seattle Genetics, Bothell, WA; City of Hope Comprehensive Cancer Center, Duarte, CA

Background: Older patients and those with significant comorbidities have not attained outcomes seen in younger patients with classical Hodgkin lymphoma (cHL) and CD30-expressing peripheral T-cell lymphoma (PTCL). Five-year progression-free survival (PFS) was 30%–45% in older HL patients treated with combination chemotherapy versus 75%–80% in younger patients (Evens 2008; Proctor 2009). Similarly, when adjusted for age, a Charleston Comorbidity Index $2 was independently associated with worse overall survival (HR=1.63) and PFS (HR=1.54) (Ellin 2018). Brentuximab vedotin (BV, ADCETRIS), a CD30-directed antibody-drug conjugate, has robust activity in cHL patients refractory to several lines of chemotherapy. BV monotherapy in 27 cHL patients aged $60 years had a 92% objective response rate (ORR) and 73% achieved complete remission (Forero-Torres, 2015). BV was also active and well-tolerated in CD30-expressing PTCL patients with relapsed or refractory disease (Horwitz 2014). Frontline BV monotherapy may have the potential to be an active and well-tolerated treatment for cHL and PTCL patients who are older or have significant comorbidities, which are populations with high unmet need. Methods: This phase II, open-label study, SGN35-015 (NCT01716806), has added 2 cohorts to evaluate the efficacy and tolerability of BV monotherapy in treatment naive patients with cHL, (Part E), or CD30-expressing PTCL (Part F, n~50 each) who are unsuitable for conventional combination therapy due to comorbidity-related factors as determined by a Cumulative Illness Rating Scale (CIRS) score $10 or dependence on others for any instrumental activities of daily living. Eligible patients must also have an Eastern Cooperative Oncology Group (ECOG) performance status #3 and measurable disease $1.5 cm per radiographic techniques. BV (1.8 mg/kg) will be administered as a single intravenous infusion on day 1 of each 2-day cycle. Patients achieving a complete remission, partial remission, or stable disease will receive up to 16 cycles of treatment. Response will be assessed by blinded independent central review of spiral CT and PET scans at Cycles 2, 6, 11, and at end of treatment to be graded per Lugano 2014. The primary objective of these cohorts is to assess ORR of frontline therapy with single-agent BV in patients who have significant comorbidities. Clinical trial information: NCT01716806. Research Sponsor: Seattle Genetics.

TPS8070 Poster Session (Board #403), Fri, 8:00 AM-11:00 AM

POLARGO: Randomized Phase III study of polatuzumab vedotin plus rituximab, gemcitabine, and oxaliplatin (R-GemOx) in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL).

Corinne Haioun, Matthew J. Matasar, Juan-Manuel Sancho, Andreas Viardot, Juana Hernandez, Thomas Perretti, Andrew McMillan; Lymphoı¨d Malignancies Unit, Groupe Hospitalier Henri Mondor, Creteil ´ Cedex, France; Memorial Sloan Kettering Cancer Center, New York, NY; HU Germans Trias I Pujol, Barcelona, Spain; University Hospital of Ulm, Ulm, Germany; F. Hoffmann-La Roche Ltd, Basel, Switzerland; Centre for Clinical Haematology, Nottingham University Hospitals NHS Trust, Notting- ham, United Kingdom

Background: The antibody-drug conjugate polatuzumab vedotin (pola; POLIVY) targets CD79b on B-cell malignancies. Pola plus bendamustine and rituximab (BR) has significantly improved efficacy vs BR alone in patients (pts) with R/R DLBCL. As a result, pola-BR was approved by the FDA for pts with R/R DLBCL after $2 prior therapies. This year, the EU granted conditional marketing authorization for pola- BR in pts with stem cell transplant (SCT)-ineligible R/R DLBCL. A range of therapies are used for R/R DLBCL; one recommended option is R-GemOx. Platinum-based chemotherapies such as oxaliplatin are a preferred salvage therapy. In the POLARGO study, the safety and efficacy of pola-R-GemOx vs R- GemOx alone will be assessed in pts with R/R DLBCL. Methods: POLARGO (MO40598; NCT04182204) is a multicenter, open-label, Phase III study, comprising a safety run-in stage (pola-R-GemOx; n=10) and a randomized controlled trial (RCT) stage (pola-R-GemOx vs R-GemOx alone; expected n=206). Pts must have histologically confirmed R/R DLBCL and ECOG PS of 0–2. Exclusion criteria include prior allogeneic SCT and/or planned autologous/allogeneic SCT, and baseline grade .1 peripheral neuropathy (PN). Pts in the RCT stage will be recruited from 80–90 sites globally. The primary endpoint of the safety run-in stage is the safety and tolerability of pola-R-GemOx (pola, 1.8mg/kg; R, 375mg/m2; Gem, 1000mg/m2; Ox, 100mg/m2) administered in 21-day cycles, with a focus on PN. In the RCT stage, pts will be stratified by number of prior lines of therapy, outcome of last systemic therapy and age, and randomized (1:1) to receive up to eight 21-day cycles of pola-R-GemOx or R-GemOx. The RCT stage primary endpoint is overall survival. Key secondary endpoints are independent review committee-assessed complete response (CR) and objective response rate (ORR; Lugano 2014 criteria). Other secondary efficacy endpoints include investigator-assessed best overall response, CR rate and ORR. Safety and health-related quality of life during treatment will be assessed. PET-CT and CT scans will be obtained at screening, during, and after the treatment period; follow-up will continue for up to 2 years. POLARGO is currently open and recruiting. Acknowledgment: POLARGO is sponsored by F. Hoffmann-La Roche Ltd. Third-party medical writing assistance, under the direction of Prof. Haioun, Dr McMillan and Dr Hernandez, was provided by Lucinda Sinclair of Gardiner-Caldwell Communications and was funded by F. Hoffmann-La Roche Ltd. Clinical trial information: NCT04182204. Research Sponsor: F. Hoffmann-La Roche Ltd.

TPS8071 Poster Session (Board #404), Fri, 8:00 AM-11:00 AM

Trial in progress: A phase III, randomized, open-label study comparing zanubrutinib plus rituximab versus bendamustine plus rituximab in patients with previously untreated mantle cell lymphoma (MCL).

Martin H. Dreyling, Constantine Si Lun Tam, Michael Wang, Stephen Douglas Smith, Marco Ladetto, Huiqiang Huang, Rebecca L. Elstrom, Melannie Co, Eric Holmgren, Jane Huang, Steven Le Gouill; University Hospital Grobhadern, Ludwig Maximilians-University, Munich, Germany; Peter MacCallum Cancer Centre, Melbourne, St Vincent’s Hospital, Fitzroy, University of Melbourne, Parkville and Royal Melbourne Hospital, Parkville, Victoria, Australia; MD Anderson Cancer Center, Houston, TX; University of Washington/Fred Hutchinson Cancer Research Center, Seattle, WA; Az Ospedaliera Santi Antonio e Biagio e Cesare Arrigo, Alessandria, Italy; Sun Yat-sen University Cancer Center, Guangdong Province, China; BeiGene USA, Inc., San Mateo, CA; Centre Hospitalier Universitaire de Nantes, Nantes, France

Background: Bruton tyrosine kinase (BTK) mediates B-cell proliferation, migration, and adhesion. BTK inhibition has emerged as a strategy for targeting B-cell malignancies, including MCL. Zanubrutinib is a next-generation BTK inhibitor that was designed to maximize BTK occupancy and minimize off-target inhibition of TEC- and EGFR-family kinases, with favorable pharmacokinetic and pharmacodynamic properties. Zanubrutinib monotherapy has been evaluated in 118 patients (pts) with relapsed/ refractory MCL in 2 single-arm studies: BGB-3111-206 [NCT03206970] and BGB-3111-AU-003 [NCT02343120]. The overall response rate (ORR) by independent review committee (IRC) in both trials was 84% with median durations of response of 19.5 and 18.5 months, respectively. First-line treatment for MCL has failed to cure most pts, particularly elderly or transplant-ineligible groups, and chemotherapy-based approaches result in cumulative, long-term risks. The study described herein is designed to evaluate the safety and efficacy of zanubrutinib plus rituximab versus bendamustine plus rituximab in elderly pts and pts with comorbidities with previously untreated MCL who are ineligible for stem cell transplant. Methods: This ongoing phase 3, open-label study will enroll »500 pts to be randomized 1:1, stratified by MCL International Prognostic Index score (low vs intermediate/high), age ( , 70 vs $70 years), and geographic region (North America/Europe vs Asia-Pacific). In arm A, pts will receive up to six 28-day cycles of oral zanubrutinib 160 mg twice daily in combination with intravenous (IV) rituximab 375 mg/m2 on day 1 of each cycle. After 6 cycles, zanubrutinib will continue as a monotherapy until progressive disease, unacceptable toxicity, or withdrawal of consent. In arm B, pts will receive up to six 28-day cycles of IV bendamustine 90 mg/m2 on days 1 and 2 of each cycle and rituximab 375 mg/m2 on day 1 of each cycle, followed by observation. Eligible pts must have histologically confirmed MCL and be aged $70 years, or 65-69 years with defined comorbidities. Disease response will be assessed per the 2014 Lugano Classification for non-Hodgkin lymphoma. The primary endpoint is progression-free survival (PFS) determined by IRC. Key secondary end points include PFS by investigator assessment, ORR, time to and duration of response, overall survival, and safety. Recruitment is ongoing. Clinical trial information: NCT04002297. Research Sponsor: BeiGene.

TPS8072 Poster Session (Board #405), Fri, 8:00 AM-11:00 AM

A phase I and randomized phase II etctn study of KW-0761 (Mogamulizumab) and MK- 3475 (Pembrolizumab) in relapsed and refractory diffuse large B-cell lymphoma.

Erel Joffe, Santosha Adipudi Vardhana, Anita Kumar, Mehrdad Abedi, Rasmus Hoeg, Elad Sharon, Anas Younes; Memorial Sloan Kettering Cancer Center, New York, NY; Memor Sloan-Kettering Cancer Ctr, New York, NY; University of California, Davis Comprehensive Cancer Center, Sacramento, CA; National Cancer Institute, Bethesda, MD

Background: Diffuse large B-cell lymphoma (DLBCL) escapes host immune responses via inhibition of the B2M and CD58 pathways and upregulation of PD-1 ligands. However, treatment results with PD-1 blockade have been disappointing. One potential mechanism is the recruitment of intra-tumoral regulatory T-cells (Tregs) which suppress anti-tumor immunity and inhibit NK cell cytotoxicity. Targeting regulatory T cells with the CCR4 antibody mogamulizumab (KW-0761) represents a mo- lecularly informed strategy to overcome this resistance. Mogamulizumab has been safely administered in combination with pembrolizumab (MK-3475) in patients with solid malignancies and may promote CD8 T-cell dependent effector and NK cell-dependent cytotoxicity in lymphomas. Methods: This is a multi-center NIH-ETCTN phase Ib/randomized phase II study. The phase I will evaluate the safety and tolerability of mogamulizumab in combination with pembrolizumab in patients with R/R DLBCL and determine the recommended phase II dose (RP2D). A traditional 3+3 design with a starting dose of pembrolizumab 200mg IV on day 1 of a 21-day cycle and mogamulizumab 1mg/kg IV on days 1, 8, 15 and then 1.5 mg/kg IV every 21 days. The phase II will evaluate the efficacy of the combination by PFS (primary endpoint) ORR and CR (secondary endpoints). This will be a randomized 1:1 study with allowed crossover, comparing the combination to single agent pembrolizumab Correlative studies will evaluate the association of tumor infiltrating CD8 and NK cells with response to treatment, somatic mutations in B2M and CD58 and with MHC-I expression on DLBCL cells. Functional characterization of circulating immune cells in the peripheral blood and measurement of pro and anti-inflammatory cytokines will be used to assess the levels, activation status and effector function of Tregs and circulating T cells. Inclusion criteria include measurable disease, $2 prior lines of therapy including or ineligible for autologous stem cell transplant, ECOG # 2 and normal organ function. Prior or planned allogeneic stem cell transplant, as well as prior treatment with an anti PD-1/PD-L1/CTLA4 antibody, preexisting autoimmune disease or CNS involvement by lymphoma are exclusion criteria. The study aims to enroll up to 12 patients on the phase I and up to 58 patients on the phase II and can be opened at any ETCTN participating site. To date it has been opened at two sites and is accruing the first patients for the phase I portion. Clinical trial information: NCT03309878. Research Sponsor: U.S. National Institutes of Health.

TPS8073 Poster Session (Board #406), Fri, 8:00 AM-11:00 AM

Phase I/II study of R-ICE (rituximab-ifosfamide-carboplatin-etoposide) with lenalidomide (R2-ICE) in patients with first-relapse/primary refractory diffuse large B-cell lymphoma (DLBCL) in academic and community cancer research united (ACCRU) network.

Francis Guerra-Bauman, Betsy LaPlant, William R. Macon, Thomas E. Witzig, Umar Farooq, Grzegorz S. Nowakowski, Tatyana Feldman; Mayo Clinic, Rochester, MN; University of Iowa Carver College of Medicine, Iowa City, IA; John Theurer Cancer Center, Hackensack, NJ

Background: Response rates to salvage immunochemotherapy in patients with DLBCL relapsing after or refractory (R/R DLBCL) to front line therapy remain unsatisfactory. Lenalidomide (Len) has significant single agent activity in relapsed/refractory DLBCL. The addition of lenalidomide (Len) days 1-7 to rituximab plus ifosfamide-carboplatin-etoposide (RICE) was shown to be feasible with promising efficacy in phase 1b study (Feldman T, et al. BJH, 2014). We developed phase I/II study to evaluate the safety and efficacy of the addition of Len (extended to 14 day schedule) to RICE (R2-ICE) for R/R- DLBCL patients who are candidates for stem cell transplant. Methods: The phase I portion was designed to determine the maximally tolerated dose Len in combination with RICE using the standard cohort 3+3 design. The escalation dose levels were 15 mg and 20 mg daily x 14 days. Prophylactic aspirin and growth factor support is mandatory. After 2 cycles of therapy response is evaluated with a PET/CT scan; the responding patients are eligible for 1-2 additional cycles of R2ICE as a bridging before HDC/SCT. The estimated overall response rate for two cycles of R-ICE in R/R DLBCL to RCHOP was estimated to be approximate 45%. We hypothesize that the addition of lenalidomide in the relapse setting could increase the overall response rate by approximately 20%. The one-stage design with an interim analysis being utilized in phase 2 requires 45 evaluable patients (one sided alpha = 0.09, power 90%). For Phase I, all types of B-cell lymphomas were eligible. For phase II portion only DLBCL patients are eligible per central pathology review. Other eligibility criteria include: received one line of previous anti- lymphoma therapy, $ 2 weeks from completion of prior anti-lymphoma therapy, candidate for HDC and SCT, adequate organ (creatinine clearance $ 60ml/min by Cockcroft-, total bilirubin # 2 3 ULN) and bone marrow function (ANC) $1500/mm3; platelet count $75,000/mm3). The use of steroids and/or rituximab up to 1 week prior to registration for management of symptoms is allowed. 9 patients cleared phase 1 without DLT and dose of 20 mg days 1 -14 was recommend for phase 2 part (RP2D) of the study. The phase 2 study passed interim futility analysis and accrual continues. Correlatives include cell of origin by Nanostring, Myc/bcl2 expression and by FISH and minimal residual disease. PET scans are centrally reviewed including metabolic tumor volume. Clinical trial information: NCT02628405. Research Sponsor: Celgene/BMS.

TPS8074 Poster Session (Board #407), Fri, 8:00 AM-11:00 AM

A phase II study of MT-3724, a novel CD20-targeting engineered toxin body, to evaluate safety, pharmacodynamics, and efficacy in subjects with relapsed or refractory diffuse large B-cell lymphoma.

Adolfo Enrique Diaz Duque, Tetiana Perekhrestenko, Vasile Musteata, Mamia Zodelava, Troy H. Guthrie, Thomas Strack, Christine Burnett, Sarah Wilson, Roger J. Waltzman, Tara D. Baetz, Daniel O. Persky; University of Texas Health at San Antonio, San Antonio, TX; Medical Center Named by Academician Yuriy Spizhenko (ARENSIA Exploratory Medicine Unit), Kyiv, Ukraine; Institute of Oncology, ARENSIA Ex- ploratory Medicine Unit, Chisinau, Moldova, The Republic of; ARENSIA Exploratory Medicine LLC, Tbilisi, Georgia; 21st Century Oncology, Jacksonville, FL; Molecular Templates, Inc., Jersey City, NJ; Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston, ON, Canada; University of Arizona Cancer Center, Tucson, AZ

Background: Engineered toxin bodies (ETBs) are comprised of a proprietarily engineered form of Shiga- like Toxin A subunit (SLT-A) genetically fused to antibody-like binding domains. ETBs work through novel mechanisms of action and are capable of forcing internalization, self-routing through intracellular compartments to the cytosol, and inducing potent cell-kill via the enzymatic and permanent inactivation of ribosomes. MT-3724 represents a novel ETB modality comprised of an anti-CD20 single-chain variable fragment genetically fused to SLT-A. It is capable of efficient internalization once bound to CD20 and can induce potent direct cell-kill via enzymatic ribosome inactivation. MT-3724 is currently being studied in three ongoing Phase 2 studies for relapsed or refractory diffuse large B-cell lymphoma (r/rDLBCL). Methods: The primary objective of this single-arm, Phase 2 study (NCT02361346) is to determine the efficacy of MT-3724 monotherapy in r/rDLBCL based on overall response rate (ORR), defined as the proportion of subjects with a complete/partial response according to the Lugano criteria, as assessed by independent, central review. Key secondary objectives include safety, progression-free survival, investigator-assessed ORR, duration of response, overall survival, and pharmacodynamics. Adverse events will be assessed and documented according to Common Terminology Criteria for Adverse Events version 5.0. Key eligibility criteria include adult subjects with histologically confirmed, r/rDLBCL, with $2 prior standard of care systemic NHL treatment regimens, and $1 measurable lesion. As rituximab and other CD20-targeting antibodies compete with MT-3724 for the same CD20 domain, minimum washout periods from these agents must be observed. Subjects remain eligible post stem cell transplant or chimeric antigen receptor T-cell therapy. Subjects will receive 50 mg/kg MT- 3724 IV over 1 hour on Days 1, 3, 5, 8, 10 and 12 of a 21-day treatment cycle. The anticipated sample size is N = 100. Interim analyses will be performed to confirm minimum efficacy thresholds based on the encouraging data observed in the completed phase 1 portion of the study [Hamlin et al. Blood 2019;134(Suppl 1):4098]. Multiple global sites are enrolling subjects. Clinical trial information: NCT02361346. Research Sponsor: Molecular Templates, Inc.

TPS8075 Poster Session (Board #408), Fri, 8:00 AM-11:00 AM

Phase I study of radiotherapy (RT) & durvalumab in relapsed/refractory diffuse large B-cell lymphoma (DLBCL) & follicular lymphoma (FL): The RADD study.

Eliza Anne Hawkes, Kate Manos, Geoffrey Chong, Jodie Palmer, Michael Patrick MacManus, Colm Keane, Andrew Mark Scott, Jake Shortt, David Ritchie, Leonid Churilov, Laura Johnston, Tom Witkowski, Allison Anne Barraclough, Sze Ting Lee, Wendi Lin, Rachel Koldej, Richard Khor; Austin Health and Olivia Newton-John Cancer Research Institute, Heidelberg, Australia; Austin Health, Heidelberg, Australia; Olivia Newton-John Cancer Research Institute, Heidelberg, Australia; Peter MacCallum Cancer Inst, East Melbourne, VIC, Australia; Princess Alexandra Hospital, Woolloongabba, Australia; Monash University and Monash Health, Melbourne, Australia; Peter MacCallum Cancer Centre & Royal Melbourne Hospital, Melbourne, Australia; University of Melbourne, Melbourne, Australia; Australian Cancer Research Foundation at Royal Melbourne Hospital, Melbourne, Australia

Background: Most DLBCL & FL responds well to first line treatment, yet relapsed disease outcomes are poor. PD1/PDL1 inhibitors yield high response rates in some lymphomas, but single agent therapy in heavily pre-treated pts are disappointing. RT stimulates anti-tumor immunity through several mechanisms and may enhance response to immune checkpoint inhibition (ICI). Concurrent ICI & RT is synergistic in preclinical studies & solid tumors, improving local & distant (abscopal) response. RT to multiple disease sites may broaden the spectrum of tumor antigen release and overcome clonal variation between disease sites to further augment the immune response. Methods: RaDD (NCT03610061) is a phase I, 3+3 dose escalation study to determine the safety profile of escalating dose & number of sites of RT in combination with Durvalumab (anti-PD-L1 antibody) in RR DLBCL & FL. Eligible pts (i.e. $1 prior therapy, ineligible for auto-SCT, no contraindication to PDL1i) receive 5 fractions of external beam RT to target site(s). 5 RT dose & site levels are included (dose range 2.5Gy- 20Gy to 1-3 sites). Durvalumab 1500mg IV commences day 2 of RT and continues 4-weekly until confirmed disease progression. The DLT period is 28 days from start of RT. Primary endpoint is the recommended phase two dose (RP2D) of RT in combination with durvalumab. Secondary endpoints include response rates, PFS & OS. Correlative studies will examine the tumour-immune system interaction; an exploratory PET substudy with novel tracers for durvalumab (89Zr-Durvalumab) & CD8+ T cells (89Zr -Df-IAB22M2C) will also be performed. Projected enrollment for determination of maximum tolerated dose (MTD) & RP2D is 6-30 pts pending toxicity. Recruitment will continue to 36 pts for secondary endpoint analysis. 9 pts are enrolled across cohorts 1-3 to date. Clinical trial information: NCT03610061. Research Sponsor: Victorian Cancer Agency (grant funding - TRP16006), Pharmaceutical/Biotech Company.