18th International Myeloma Workshop 2021 September 8-11, 2021 OAB-001 12Department of Medicine/Haematology, NUI, Overall Survival and Progression-free Survival Galway, Republic of Ireland by Treatment Duration With Daratumumab + 13CHU de Toulouse, IUCT-O, Université de Lenalidomide/Dexamethasone in Transplant- Toulouse, UPS, Service d’Hématologie, ineligible Newly Diagnosed Multiple Myeloma: Toulouse, France Phase 3 MAIA Study 14Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada Philippe Moreau1, Thierry Facon2, Shaji 15Department of Oncology, Hematology and Kumar3, Torben Plesner4, Robert Z. Orlowski5, Bone Marrow Transplantation, University Nizar Bahlis6, Supratik Basu7, Hareth Nahi8, Medical Center Hamburg-Eppendorf, Hamburg, Cyrille Hulin9, Hang Quach10, Hartmut Germany Goldschmidt11, Michael O’Dwyer12, Aurore 16Florida Cancer Specialists, St. Petersburg, FL, Perrot13, Christopher Venner14, Katja Weisel15, USA Joseph R. Mace16, Noopur Raje17, Mourad 17Massachusetts General Hospital Cancer Center Tiab18, Margaret Macro19, Laurent Frenzel20, 18CHD Vendée, La Roche sur Yon, France Xavier Leleu21, Huiling Pei22, Brenda Tromp23, 19Centre Hospitalier Universitaire (CHU) de Maria Delioukina24, Saad Z. Usmani25 Caen, Caen, France 20Department of Clinical Haematology, Hopital 1University Hospital Hôtel-Dieu Necker-Enfants Malades, Paris, France 2University of Lille, CHU Lille, Service des 21Service d'Hématologie et Thérapie Cellulaire, Maladies du Sang, Lille, France CHU and CIC Inserm 1402, Poitiers Cedex, 3Department of Hematology, Mayo Clinic France Rochester, Rochester, MN, USA 22Janssen Research & Development, LLC, 4Vejle Hospital and University of Southern Titusville, NJ, USA Denmark, Vejle, Denmark 23Janssen Research & Development, LLC, 5Department of Lymphoma and Myeloma, The Leiden, The Netherlands University of Texas MD Anderson Cancer 24Janssen Research & Development, LLC, Center, Houston, TX, USA Spring House, PA, USA 6Arnie Charbonneau Cancer Research Institute, 25Levine Cancer Institute/Atrium Health, University of Calgary, Calgary, AB, Canada Charlotte, NC, USA 7The Royal Wolverhampton Hospitals NHS Trust and University of Wolverhampton, Introduction: In the primary analysis of MAIA, Wolverhampton, United Kingdom daratumumab (DARA) plus lenalidomide and 8Karolinska Institute, Department of Medicine, dexamethasone (D-Rd) reduced the risk of Division of Hematology, Karolinska University disease progression or death by 44% vs Hospital at Huddinge, Stockholm, Sweden lenalidomide and dexamethasone (Rd) in 9Department of Hematology, Hôpital Haut transplant-ineligible patients (pts) with newly Lévêque, University Hospital, Pessac, France diagnosed multiple myeloma (NDMM). Here, 10University of Melbourne, St Vincent’s we report the updated efficacy and safety of D- Hospital, Melbourne, Australia Rd vs Rd after almost 5 years of median follow- 11Multiple Myeloma Section, Department of up from the prespecified interim overall survival Medicine V, University Hospital Heidelberg; (OS) analysis of MAIA (NCT02252172). and National Center for Tumor Diseases (NCT) Methods: Pts with NDMM ineligible for high- dose chemotherapy and autologous stem cell transplantation due to age ≥65 years or comorbidities were randomized 1:1 to D-Rd or Rd. All pts received 28-day cycles of Rd (R: 25 mg PO once daily on Days 1-21; d: 40 mg PO on Days 1, 8, 15, 22) ± DARA (16 mg/kg IV QW for Cycles 1-2, Q2W for Cycles 3-6, and Q4W thereafter). All pts were treated until disease progression/unacceptable safety events. The primary endpoint was progression-free survival (PFS). Results: 737 pts (D-Rd, 368; Rd, 369) enrolled and baseline characteristics were well balanced. Median age was 73 (range, 45-90) years. At a 56.2-month median follow-up, a significant 32% reduction in the risk of death was observed with D-Rd vs Rd. Median OS was not reached (NR) in either arm (HR, 0.68; 95% CI, 0.53-0.86; P=0.0013 [crossing the prespecified stopping boundary of P=0.0414]); estimated 5-year OS rates were 66.3% with D-Rd and 53.1% with Rd. The updated median PFS was NR with D-Rd vs 34.4 months with Rd (HR, 0.53; 95% CI, 0.43- 0.66; PPP=0.2480); a PFS benefit was not observed with D-Rd vs Rd in pts who received P=0.3579). No new safety concerns were identified with longer follow-up. The most common grade 3/4 treatment-emergent adverse event was neutropenia (D-Rd, 54.1%; Rd, 37.0%). Conclusions: After ~5 years of follow-up, D-Rd vs Rd showed a significant and clinically meaningful PFS and OS improvement in transplant-ineligible pts with NDMM. Additionally, D-Rd showed a greater PFS benefit vs Rd among pts treated for ≥18 months than among pts treated for shorter durations. Taken together with real-world data indicating that many transplant-ineligible pts do not receive a second line of therapy, the favorable benefit- risk profile observed in MAIA supports the frontline use of D-Rd in transplant-ineligible pts with NDMM. OAB-002 ineligible high-risk patients from MAIA and Daratumumab improves depth of response and ALCYONE RCTs, using longer follow-up data, progression free survival in transplant-ineligible, adjusting for patient-level imbalances in baseline high-risk, newly diagnosed multiple myeloma characteristics, and evaluating additional (NDMM) efficacy endpoints. Methods: A stratified pooled analysis of Andrzej Jakubowiak1, Shaji Kumar2, Rohan patient-level data for ASCT-ineligible NDMM Medhekar3, Huiling Pei4, Patrick Lefebvre5, patients with high cytogenetic risk [i.e., Shuchita Kaila6, Jianming He7, Marie-Helene del(17p), t(4;14), or t(14;16)] from MAIA and Lafeuille8, Annelore Cortoos9, Anil Londhe10, ALCYONE RCTs was conducted, adjusting for Panagiotis Mavros11, Thomas Lin12, Saad Z. cytogenetic abnormality subtype, baseline Usmani13 performance status, International Staging System stage, type of multiple myeloma, and 1University of Chicago, Chicago, IL, USA renal impairment. The impact of Dara on PFS 2Department of Hematology, Mayo Clinic and rates of complete response or better (≥CR), Rochester, Rochester, MN, USA minimal residual disease (MRD)-negative CR, 3Janssen Scientific Affairs, LLC very good partial response or better (≥VGPR), 4Janssen Research & Development, LLC, and overall response (ORR), compared to Titusville, NJ, USA control treatment, was assessed using the study 5Analysis Group, Inc identifier as the stratification factor. 6Janssen Scientific Affairs, LLC Results: There were 101 patients in Dara and 89 7Janssen Scientific Affairs, LLC patients in the control cohort. Median follow-up 8Analysis Group, Inc was 43.7 months. In the adjusted analysis, the 9Janssen Scientific Affairs, LLC, Horsham, PA, risk of progression or death was reduced by 41% USA in the Dara cohort vs control (hazard ratio [95% 10Janssen R&D US confidence interval (CI)] = 0.59 [0.41-0.85]). At 11Janssen Scientific Affairs, LLC 36 months, the proportion of patients who did 12Janssen Scientific Affairs, LLC, Horsham, PA, not progress and were still alive was 41.3% in USA the Dara and 19.9% in the control cohort. 13Levine Cancer Institute/Atrium Health, Deeper response was observed in the Dara Charlotte, NC, USA cohort with higher rates, and adjusted odd ratios (95% CI) for ≥CR (41.6% vs. 22.5%; 2.63 [1.34- Introduction: Patients with high-risk NDMM 5.16]), MRD-negative CR (24.8% vs. 5.6%; who are ineligible for autologous stem cell 5.50 [1.97-15.34]), ≥VGPR (75.3% vs. 46.1%; transplant (ASCT) have limited first-line 4.03 [2.09-7.78]), and ORR (92.1% vs. 74.2%; treatment options, and new regimens to improve 4.88 [1.94-12.27]) compared to control. their outcomes are needed. Daratumumab (Dara) Conclusion: Addition of Dara to backbone is approved in combination with lenalidomide regimens resulted in 41% reduction in risk of and dexamethasone (D-Rd) and in combination progression or death among ASCT-ineligible with bortezomib, melphalan, and prednisone (D- high-risk NDMM patients. Additionally, patients VMP) in ASCT-ineligible NDMM patients, in the Dara cohort had a two-fold higher based on the randomized clinical trials (RCTs), likelihood of achieving ≥CR and a five-fold MAIA and ALCYONE, respectively. A recent higher likelihood of achieving MRD-negative meta-analysis of data from these two RCTs CR relative to control. This study provides along with ASCT-eligible patients from the additional evidence that the use of Dara based CASSIOPEIA RCT demonstrated that first-line treatment benefits high-risk NDMM incorporation of Dara was associated with patients. improved progression free survival (PFS) in high-risk NDMM patients. The current study builds upon these findings by focusing on the more homogenous population of ASCT- OAB-003 MRD rates following novel induction and CARDAMON:Carfilzomib (K) maintenance consolidation (cons) strategies. K maintenance following Autologous Stem Cell Transplant represents an alternative strategy to lenalidomide (ASCT) or carfilzomib-cyclophosphamide- maintenance. The CARDAMON trial dexamethasone (KCd) consolidation for newly investigated K maintenance following KCd diagnosed (NDTE) multiple myeloma (MM) induction plus either ASCT or KCd cons. Methods: NDTE pts received 4 x KCd Rakesh Popat1, William Wilson2, Marquita induction (K 20/56 mg/m2 biweekly, C 500 mg Camilleri3, Ruth De Tute4, Gavin Pang5, Richard D 1,8,15, d 40mg weekly) before 1:1 Jenner6, Tushhar Dadaga7, Sumaiya Kamora8, randomisation to ASCT or 4 x KCd cons Matthew Streetly9, Karthik Ramasamy10, followed by 18 cycles K maintenance (56mg/m2 Elizabeth Phillips11, Mike