February 2014 Volume 12, Issue 2, Supplement 6 A SPECIAL MEETING REVIEW EDITION Highlights in Lymphoma From the 2013 American Society of Hematology Annual Meeting and Exposition A Review of Selected Presentations From the 2013 American Society of Hematology Annual Meeting and Exposition • December 7-10, 2013 • New Orleans, Louisiana Special Reporting on: • A Phase 2 Study of Brentuximab Vedotin in Patients With Relapsed or Refractory CD30-Positive Non-Hodgkin Lymphomas: Interim Results in Patients With DLBCL and Other B-Cell Lymphomas • A Phase I Study of Panobinostat in Combination With ICE (Ifosfamide, Carboplatin and Etoposide) in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma (cHL) • FDG-PET Adapted Sequential Therapy With Brentuximab Vedotin and Augmented ICE Followed by Autologous Stem Cell Transplant for Relapsed and Refractory Hodgkin Lymphoma • Mature Response Data From a Phase 2 Study of PI3K-Delta Inhibitor Idelalisib in Patients With Double (Rituximab and Alkylating Agent)-Refractory Indolent B-Cell Non-Hodgkin Lymphoma (iNHL) • Phase II Trial of Brentuximab Vedotin for CD30+ Cutaneous T-Cell Lymphomas and Lymphoprolif- erative Disorders • Lenalidomide in Combination With R-CHOP (R2-CHOP) in Patients With High Burden Follicular Lymphoma: Phase 2 Study • Reduced-Intensity Conditioning (RIC) and Allogeneic Stem Cell Transplantation (allo-SCT) for Relapsed/Refractory Hodgkin Lymphoma (HL) in the Brentuximab Vedotin Era: Favorable Overall and Progression-Free Survival (OS/PFS) With Low Transplant-Related Mortality (TRM) • Combination Biologic Therapy Without Chemotherapy as Initial Treatment for Mantle Cell Lym- phoma: Multi-Center Phase II Study of Lenalidomide Plus Rituximab PLUS Meeting Abstract Summaries With Expert Commentary by: Nancy L. Bartlett, MD Professor of Medicine Koman Chair in Medical Oncology Washington University School of Medicine St Louis, Missouri ON THE WEB: hematologyandoncology.net Indexed through the National Library of Medicine (PubMed/MEDLINE), PubMed Central (PMC), and EMBASE PHASE 3 TRIAL NOW RECRUITING Assessing brentuximab vedotin in Frontline Peripheral T-cell Lymphomas Consider ECHELON-2 when making a treatment plan Patients Investigational arm † Endpoints CD30-positive mature (peripheral) A+CHP regimen (6-8 cycles) T-cell lymphomas, including Brentuximab vedotin Primary endpoint systemic ALCL (N = 300)* 1.8 mg/kg IV on day 1 of each 21-day cycle, plus placebo • Progression-free Select inclusion criteria: replacement for vincristine survival (PFS) • Newly diagnosed • Measurable disease, as defined by both of the Standard arm Secondary endpoints following: • Overall survival † – FDG-avid disease by PET CHOP regimen (6-8 cycles) • Overall response rate 2 – CT tumor burden ≥1.5 cm Vincristine 1.4 mg/m IV on • Safety and tolerability • ECOG performance day 1 of each 21-day cycle, status 0 to 2 plus placebo replacement for brentuximab vedotin * Eligible subtypes include anaplastic lymphoma kinase (ALK)–positive systemic anaplastic large cell lymphoma (ALCL) with an International Prognostic Index (IPI) score of ≥2; ALK-negative systemic ALCL; peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS); angioimmunoblastic T-cell lymphoma (AITL); adult T-cell leukemia/lymphoma (ATLL); enteropathy-associated T-cell lymphoma (EATL); and hepatosplenic T-cell lymphoma. † Cyclophosphamide 750 mg/m2 and doxorubicin 50 mg/m2 will be administered IV on day 1; 100 mg oral prednisone will be administered on days 1-5 of each 21-day cycle. To learn more about ECHELON-2 Eligible patients must or refer a patient: be treatment-naïve • Contact Seattle Genetics Medical Information at 866.333.7436 (US only) STOP BEFORE • E-mail [email protected] CHOP • Visit clinicaltrials.gov (NCT01777152) seattlegenetics.com MILLENNIUM and are registered trademarks Seattle Genetics and are US registered trademarks of Seattle Genetics, Inc. of Millennium Pharmaceuticals, Inc. Other trademarks are property of their respective owners. Other trademarks are property of their respective owners. © 2013 Seattle Genetics, Inc., Bothell, WA 98021 Millennium Pharmaceuticals, Inc., Cambridge, MA 02139 All rights reserved. Printed in USA USM/BVM/2013/0235a Copyright © 2013, Millennium Pharmaceuticals, Inc. All rights reserved. 20808_sgn35_fa1_ech_bld.indd 1 1/29/14 12:07 PM PHASE 3 TRIAL HIGHLIGHTS IN LYMPHOMA FROM THE 2013 ASH ANNUAL MEETING AND EXPOSITION NOW RECRUITING A Phase 2 Study of Brentuximab Vedotin in Patients With Relapsed or Refractory CD30-Positive Non-Hodgkin Lymphomas: Interim Results in Patients With DLBCL and Other B-Cell Lymphomas Assessing brentuximab vedotin in utcomes for patients with relapsed or refractory dif- 150 Other (n=17) DLBCL (n=41) Fatigue 43% Frontline Peripheral T-cell Lymphomas fuse large B-cell lymphoma CR O(DLBCL) remain poor; autologous stem 100 cell transplant (ASCT) yields limited Nausea 43% 50 Consider ECHELON-2 when making a treatment plan efficacy in the rituximab era, and there is Grade 1/2 no standard of care for patients who are 81% of patients achieved tumor reduction 0 Vomiting 29% Grade 3 Patients Investigational arm ineligible for transplant.1 Brentuximab Tumor Size Tumor Grade 4 vedotin is an antibody-drug conjugate † Endpoints -50 CD30-positive mature (peripheral) A+CHP regimen (6-8 cycles) consisting of a CD30-directed mono- Febrile neutropenia 10% T-cell lymphomas, including Brentuximab vedotin clonal antibody linked with the micro- Baseline) From (% Change Primary endpoint -100 systemic ALCL (N = 300)* 1.8 mg/kg IV on day 1 of each tubule-disrupting agent monomethyl Anemia 24% 5% • Progression-free Individual Patients (n=58) Major Toxicities 21-day cycle, plus placebo auristatin E (MMAE). Brentuximab Select inclusion criteria: replacement for vincristine survival (PFS) vedotin has demonstrated high response • Newly diagnosed Neutropenia 5% 10% 57% rates in patients with CD30-expressing Figure 1. Interim results from a phase 2 study of brentuximab vedotin in patients • Measurable disease, as defined by both of the Standard arm Secondary endpoints B-cell malignancies, including Hodgkin with relapsed or refractory CD30-positive non-Hodgkin lymphomas showed that 5% 10% 81% (84% in A, 50% in B) following: • Overall survival lymphoma and systemic anaplastic large approximately 81% of patients had some degree of tumor reduction. CR, complete Thrombocytopenia † 2,3 response; DLBCL, diffuse large B-cell lymphoma. Adapted from Bartlett NB et al. ASH – FDG-avid disease by PET CHOP regimen (6-8 cycles) cell lymphoma. Recent studies indicate • Overall response rate abstract 848. Blood. 2013;122(21 suppl).6 0 10 20 30 40 50 60 70 80 90 100 – CT tumor burden ≥1.5 cm Vincristine 1.4 mg/m2 IV on that between 14% and 25% of DLBCLs • Safety and tolerability Patients With Events (%) • ECOG performance day 1 of each 21-day cycle, express CD30, including both activated leukemia. The median age was 63 years In the study, brentuximab vedotin plus placebo replacement for status 0 to 2 B-cell type and germinal center subtypes, (range, 17-85 years) amongWeekly patients BV x2was cycles associated46 with enrolled an (45 overall eligible) response brentuximab vedotin and CD30 expression is associated with with DLBCL and 36 years (range, 16-68 rate (ORR) of 42% in patients with a more favorable prognosis.4,5 years) among the other patients. Patients DLBCL, including 16% complete 30 pts 12 pts Based on these demonstrations of had received a median of 2 to 3 prior responses (CRs), and 22% in patients * Eligible subtypes include anaplastic lymphoma kinase (ALK)–positive systemic anaplastic large cell lymphoma (ALCL) with an International Prognostic 42 pts Index (IPI) score of ≥2; ALK-negative systemic ALCL; peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS); angioimmunoblastic T-cell CD30 positivity, a phase 2 study was systemic therapies, with 20% of patients with other histologies, including 11% Augmented ICE x2 (11 pts) lymphoma (AITL); adult T-cell leukemia/lymphoma (ATLL); enteropathy-associated T-cell lymphoma (EATL); and hepatosplenic T-cell lymphoma. undertaken evaluating brentuximab receiving a prior ASCT.cycles The majority of CRs. The median durations of response vedotin in patients with CD30-positive patients (74% of those with DLBCL and and CR were 5.8 months and 11.5 † 2 2 100 Cyclophosphamide 750 mg/m and doxorubicin 50 mg/m will be administered IV on day 1; 100 mg oral prednisone will be administered on days 1-5 relapsed or refractory non-Hodgkin lym- 89% of other patients) were refractory to months, respectively, in the DLBCL Median PFS, 11 months of each 21-day cycle. HDT/ASCT phoma (NHL). Results were presented frontline therapy, and 82% and 72% of group and 5.0 months and not reached 21 pts 39 pts transplanted at the 2013 American Society of Hema- patients, respectively,8 pts were refractory to in other patients. Median progression- 75 (1 lost to follow-up) Disease status pretransplant: tology (ASH) meeting by Dr Nancy the most recent prior therapy. free survival (PFS)-34 Deauville was 4.0 2 (2 monthsafter IFRT) in the Bartlett.6 Patients were required to be at Patients were enrolled based on 7 ptsDLBCL group-2 Deauville and 2.9 3 months in other To learn more about ECHELON-2 Further treatment (5 after IFRT) -3 PR (after IFRT) Eligible patients must least 12 years old and to have an Eastern CD30 positivityaccording as demonstrated to treating by patients. Patients received a median of 4 or refer a patient: physician 50 be treatment-naïve Cooperative