-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

4553 Daratumumab Plus Lenalidomide and Dexamethasone in Patients with Transplant-Ineligible Newly Diagnosed Multiple Myeloma: Maia Age Subgroup Analysis

Program: Oral and Poster Abstracts
Session: 653. Myeloma and Plasma Cell Dyscrasias: Prospective Therapeutic Trials: Poster III
Hematology Disease Topics & Pathways:
Research, clinical trials, Biological therapies, adult, Clinical Research, Plasma Cell Disorders, Diseases, Therapies, Lymphoid Malignancies, Monoclonal Antibody Therapy, Study Population, Human, Minimal Residual Disease
Monday, December 12, 2022, 6:00 PM-8:00 PM

Thierry Facon1*, Shaji K Kumar, MD2, Katja C. Weisel, MD3, Saad Usmani, MD4, Philippe Moreau, MD5*, Torben Plesner6, Robert Z. Orlowski, MD, PhD7, Nizar Jacques Bahlis, MD8, Supratik Basu9*, Hareth Nahi10*, Cyrille Hulin11*, Hang Quach12, Michael O'Dwyer, MD13, Aurore Perrot, MD, PhD14*, Christopher P. Venner15*, Noopur Raje, MD16, Mourad Tiab17*, Margaret Macro, MD18*, Laurent Frenzel19*, Xavier Leleu, MD, PhD20, Huiling Pei, PhD21*, Robin Carson22, Fredrik Borgsten23* and Hartmut Goldschmidt, MD24

1University of Lille, CHU Lille, Service des Maladies du Sang, Lille, France
2Department of Hematology, Mayo Clinic Rochester, Rochester, MN
3Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
4Memorial Sloan Kettering Cancer Center, New York, NY
5Hematology Department, University Hospital Hôtel-Dieu, Nantes, France
6Vejle Hospital and University of Southern Denmark, Vejle, Denmark
7Department of Lymphoma and Myeloma, MD Anderson Cancer Center, Houston, TX
8Arnie Charbonneau Cancer Research Institute, University of Calgary, Calgary, AB, Canada
9Royal Wolverhampton NHS Trust and University of Wolverhampton, CRN West Midlands, NIHR, Wolverhampton, United Kingdom
10Karolinska Institute, Department of Medicine, Division of Hematology, Karolinska University Hospital at Huddinge, Stockholm, Sweden
11Department of Hematology, Hôpital Haut Lévêque, University Hospital, Pessac, France
12University of Melbourne, St. Vincent’s Hospital, Melbourne, VIC, Australia
13Department of Medicine/Haematology, NUI, Galway, Ireland
14CHU de Toulouse, IUCT-O, Université de Toulouse, UPS, Service d’Hématologie, Toulouse, France
15Department of Medical Oncology, Cross Cancer Institute, University of Alberta and BC Cancer – Vancouver Centre Group, Alberta, Canada
16Center for Multiple Myeloma, Massachusetts General Hospital Cancer Center, Boston, MA
17CHD Vendée, La Roche sur Yon, France
18Centre Hospitalier Universitaire (CHU) de Caen, Caen, France
19Hôpital Necker-Enfants Malades, Paris, France
20CHU Poitiers, Hôpital la Milétrie, Poitiers, France
21Janssen Research & Development, LLC, Titusville, NJ
22Janssen Research & Development, Spring House, PA
23Janssen Research & Development, Raritan, NJ
24National Center for Tumor Diseases (NCT), University Clinic of Heidelberg, Internal Medicine V, Heidelberg, Germany

Introduction: Daratumumab (DARA) is a human IgGκ monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action. DARA is approved in combination with standard of care in patients (pts) with newly diagnosed multiple myeloma (NDMM) and as monotherapy and in combination with standard of care for pts with relapsed/refractory multiple myeloma. In the randomized, phase 3 MAIA study (NCT02252172), DARA plus lenalidomide and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) alone was evaluated in transplant-ineligible pts with NDMM. In the primary analysis of MAIA (median follow-up, 28.0 months), D-Rd significantly improved progression-free survival (PFS) versus Rd alone (Facon T, N Engl J Med 2019). Additionally, D-Rd significantly prolonged PFS versus Rd for pts aged ≥75 years (median, not reached [NR] vs 31.9 months; hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.44-0.92; P = 0.0146; Usmani SZ, ASCO 2019). In an analysis of overall survival (OS; median follow-up, 56.2 months), D-Rd showed a significant reduction in the risk of death versus Rd alone (HR, 0.68; 95% CI, 0.53-0.86; P = 0.0013; Facon T, Lancet Oncol 2021). Here, we present a subgroup analysis of MAIA pts aged <75 years, <70 years, and ≥70 to <75 years.

Methods: Pts with NDMM ineligible for high-dose chemotherapy with autologous stem cell transplant were randomized 1:1 to receive D-Rd or Rd alone. All pts received 28-day cycles of lenalidomide (R: 25 mg orally on Days 1-21) and dexamethasone (d: 40 mg orally on Days 1, 8, 15, and 22) with or without DARA (16 mg/kg intravenously once weekly in Cycles 1-2, once every 2 weeks in Cycles 3-6, and once every 4 weeks thereafter) until disease progression or unacceptable toxicity. The primary endpoint was PFS. Key secondary endpoints included overall response rate (ORR), OS, and minimal residual disease (MRD)–negativity rate (10–5 sensitivity, clonoSEQ® version 2.0).

Results: Of 737 randomized pts (D-Rd, n = 368; Rd, n = 369), 416 (56%) pts were aged <75 years (D-Rd, n = 208; Rd, n = 208), 155 (21%) pts were aged <70 years (D-Rd, n = 78; Rd, n = 77), and 261 (35%) pts were aged ≥70 to <75 years (D-Rd, n = 130; Rd, n = 131). At a median follow-up of 64.5 months, PFS was improved for pts receiving D-Rd versus Rd who were aged <75 years (median, NR vs 37.5 months; HR, 0.52; 95% CI, 0.39-0.68; P <0.0001; Figure A), <70 years (median, NR vs 39.2 months; HR, 0.35; 95% CI, 0.21-0.56; P <0.0001), and ≥70 to <75 years (median, 61.9 vs 37.5 months; HR, 0.64; 95% CI, 0.45-0.89; P = 0.0079; Figure B). The estimated 60-month PFS rates were higher for pts receiving D-Rd versus Rd across all subgroups: <75 years (57.4% vs 33.6%), <70 years (67.2% vs 28.7%), and ≥70 to <75 years (51.6% vs 36.6%). OS was also improved for pts receiving D-Rd versus Rd who were aged <75 years (HR, 0.59; 95% CI, 0.43-0.83; P = 0.0017), <70 years (HR, 0.50; 95% CI, 0.27-0.90; P = 0.0179), and ≥70 to <75 years (HR, 0.64; 95% CI, 0.43-0.96; P = 0.0274). The estimated 60-month OS rates were higher for pts receiving D-Rd versus Rd across all subgroups: <75 years (73.9% vs 58.8%), <70 years (79.9% vs 61.7%), and ≥70 to <75 years (70.3% vs 57.0%). The ORR was higher for D-Rd versus Rd in pts aged <75 years (95.2% vs 81.7%; P <0.0001), <70 years (93.6% vs 80.5%; P = 0.0156), and ≥70 to <75 years (96.2% vs 82.4%; P = 0.0004). Increased rates of MRD negativity (10–5) were observed with D-Rd versus Rd in pts aged <75 years (36.1% vs 12.0%; odds ratio [OR], 4.13; 95% CI, 2.49-6.84; P <0.0001), <70 years (35.9% vs 11.7%; OR, 4.23; 95% CI, 1.84-9.75; P = 0.0006), and ≥70 to <75 years (36.2% vs 12.2%; OR, 4.07; 95% CI, 2.16-7.67; P <0.0001).

Conclusions: At a median follow-up of 64.5 months, D-Rd improved efficacy versus Rd alone in subgroups of pts aged <75, <70, and ≥70 to <75 years. D-Rd demonstrated clinically meaningful benefit across all endpoints, including PFS, OS, ORR, and MRD negativity. These results, along with those presented previously (Usmani SZ, ASCO 2019), support the frontline use of DARA-based combination regimens in pts aged <75 years and ≥75 years with transplant-ineligible NDMM.

Disclosures: Kumar: Roche: Research Funding; Novartis,: Research Funding; Merck,: Research Funding; MedImmune/Astra Zeneca,: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE,: Research Funding; Adaptive,: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda,: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen,: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie,: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding; Oncopeptides: Other: Independent review committee. Weisel: Pfizer: Honoraria; Karyopharm: Consultancy, Honoraria; GSK: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria; AstraZeneca: Honoraria; Adaptive Biotech: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Novartis: Honoraria; BMS/Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Oncopeptides: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Stemline: Honoraria. Usmani: AbbVie, Amgen, BMS, Celgene, EdoPharma, Genentech, Gilead, GSK, Janssen Pharmaceuticals, Oncopeptides, Sanofi, Seagen Inc., formerly Seattle Genetics, Inc., Secura Bio, Inc., SkylineDX, Takeda, TeneoBio , Amgen, Array Biopharma, BMS, Celgene, GSK, Janssen: Research Funding; Amgen, Array Biopharma, BMS, Celgene, GSK, Janssen Pharmaceuticals, Merck, Pharmacyclics, Sanofi, Seagen Inc., formerly Seattle Genetics, Inc., SkylineDX, Takeda: Consultancy; Amgen, BMS, Janssen Pharmaceuticals, Sanofi: Speakers Bureau. Moreau: AbbVie, Amgen, Celgene, Janssen, Oncopeptides, Sanofi: Honoraria. Plesner: Janssen, Genmab, Celgene, Takeda, Oncopeptides, Genentech, AbbVie, Roche, Bristol Myers Squibb: Research Funding; Janssen, Celgene, Takeda, Oncopeptides, Genentech, CSL Behring, AbbVie: Membership on an entity's Board of Directors or advisory committees. Orlowski: Asylia Therapeutics, Inc.: Current equity holder in private company; Abbvie, BioTheryX, Inc., Bristol-Myers Squibb, Janssen Biotech, Karyopharm Therapeutics, Inc., Meridian Therapeutics, Monte Rosa Therapeutics, Neoleukin Corporation, Oncopeptides AB, Regeneron Pharmaceuticals, Inc., Sanofi-Aventis, and Takeda Pharmaceutic: Honoraria, Membership on an entity's Board of Directors or advisory committees; CARsgen Therapeutics, Celgene/Bristol Myers Squibb, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda Pharmaceuticals North America, Inc.: Research Funding; Asylia Therapeutics, Inc., BioTheryX, Inc., Heidelberg Pharma, Inc.: Research Funding. Bahlis: Amgen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria; Karyopharm Therapeutics: Consultancy, Honoraria; Takeda: Consultancy; Forus: Consultancy, Honoraria; GSK: Consultancy, Other; Genentech: Consultancy; Sanofi: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding. Basu: Sanofi: Honoraria, Other: advisory board; Sanofi, Pfizer, BMS: Consultancy, Speakers Bureau. Nahi: Genmab: Current Employment. Hulin: Amgen: Honoraria; BMS: Honoraria; GSK: Honoraria; Takeda: Honoraria; Sanofi: Honoraria; Janssen: Honoraria. Quach: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: receipt of free drug for investigator-initiated study, Research Funding; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: leadership or fiduciary role, receipt of free drug for investigator-initiated study , Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: leadership or fiduciary role , Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees, Other: receipt of free drug for investigator-initiated study, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Antengene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; CSL: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: leadership or fiduciary role, receipt of free drug for investigator-initiated study , Research Funding. O'Dwyer: Janssen: Consultancy. Perrot: Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; Abbvie: Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees. Venner: Janssen, BMS, Sanofi, FORUS, Pfizer, GSK, Amgen: Honoraria. Raje: Celgene: Honoraria; Medscape: Honoraria; Amgen: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Research to Practice: Honoraria; Two Seventy Bio: Research Funding; Massachusetts General Hospita: Current Employment; Janssen: Consultancy, Honoraria. Macro: GSK: Honoraria; Sanofi: Honoraria; Janssen: Honoraria, Other: Travel/accommodation, Research Funding; Takeda: Honoraria, Other: Travel/accommodation, Research Funding. Leleu: BMS: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; Amgen, Merck, BMS, GSK, Janssen, Oncopeptide, Takeda, Roche, Novartis, AbbVie, Sanofi, Gilead, Pfizer, Harpoon Therapeutic, Regeneron, Iteos: Consultancy, Honoraria; Takeda: Honoraria; Sanofi: Honoraria; Janssen: Honoraria; Amgen, BMS/Celgene, Janssen, Takeda, Novartis, Sanofi, Merck, Oncopeptide, Karyopharm, Roche, Abbvie, Carsgen, GSK, and Harpoon Therapeutics: Honoraria. Pei: Janssen: Current Employment, Current equity holder in publicly-traded company. Carson: Janssen: Current Employment. Borgsten: Janssen: Current Employment. Goldschmidt: Mundipharma GmbH: Research Funding; Merck Sharp and Dohme (MSD): Research Funding; Incyte: Research Funding; Molecular Partners: Research Funding; Takeda: Research Funding; Novartis: Honoraria, Research Funding; Adaptive Biotechnology: Consultancy; GlaxoSmithKline (GSK): Honoraria; Amgen, BMS, Celgene, Chugai, Dietmar-Hopp-Foundation, Janssen, Johns Hopkins University, Sanofi: Other: Grants and/or provision of Investigational Medicinal Product; Amgen, BMS, Celgene, Chugai, Janssen, Incyte, Molecular Partners, Merck Sharp and Dohme, Sanofi, Mundipharma GmbH, Takeda, Novartis: Research Funding; Amgen, BMS, Janssen, Sanofi, Takeda: Membership on an entity's Board of Directors or advisory committees; AMGEN: Consultancy, Honoraria, Other: Grants, Research Funding; BMS: Consultancy, Honoraria, Other: Grants, Research Funding; Chugai: Honoraria, Other: grants, Research Funding; Janssen: Consultancy, Honoraria, Other: Grants, Research Funding; SANOFI: Consultancy, Honoraria, Other: Grants, Research Funding; Array Biopharma: Research Funding; Amgen, BMS, Chugai, GlaxoSmithKline, Janssen, Novartis, Sanofi, Pfizer: Honoraria; Amgen, BMS, GlaxoSmithKline, Janssen, Novartis, Sanofi, Pfizer: Other: Support for attending meetings and/or travel; Celgene: Consultancy, Honoraria, Other: Grants, Research Funding; Dietmar-Hopp-Foundation: Research Funding.

*signifies non-member of ASH