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4559 Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) Alone in Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma (NDMM): Updated Analysis of the Phase 3 Maia Study

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

Shaji K Kumar, MD1, Philippe Moreau, MD2*, Nizar Jacques Bahlis, MD3, Thierry Facon4*, Torben Plesner5, Robert Z. Orlowski, MD, PhD6, Supratik Basu7*, Hareth Nahi8*, Cyrille Hulin9*, Hang Quach10, Hartmut Goldschmidt, MD11, Michael O'Dwyer, MD12, Aurore Perrot, MD, PhD13*, Christopher P. Venner14*, Katja C. Weisel, MD15, Noopur Raje, MD16, Mourad Tiab17*, Margaret Macro, MD18*, Laurent Frenzel19*, Xavier Leleu, MD, PhD20, Huiling Pei, PhD21*, Maria Krevvata22*, Robin Carson23, Fredrik Borgsten24* and Saad Usmani, MD25

1Department of Hematology, Mayo Clinic Rochester, Rochester, MN
2Hematology Department, University Hospital Hôtel-Dieu, Nantes, France
3Arnie Charbonneau Cancer Research Institute, University of Calgary, Calgary, AB, Canada
4Centre Hospitalier Universitaire (CHU) Lille, Service des Maladies du Sang, University of Lille, Lille, France
5Vejle Hospital and University of Southern Denmark, Vejle, Denmark
6Department of Lymphoma and Myeloma, MD Anderson Cancer Center, Houston, TX
7Royal Wolverhampton NHS Trust and University of Wolverhampton, CRN West Midlands, NIHR, Wolverhampton, United Kingdom
8Karolinska Institute, Department of Medicine, Division of Hematology, Karolinska University Hospital at Huddinge, Stockholm, Sweden
9Department of Hematology, Hôpital Haut Lévêque, University Hospital, Pessac, France
10St Vincent's Hospital Melbourne, University of Melbourne, Melbourne, Australia
11University Hospital Heidelberg, Internal Medicine and National Center for Tumor Diseases (NCT), Heidelberg, Germany
12Department of Medicine/Haematology, NUI, Galway, Ireland
13CHU de Toulouse, IUCT-O, Université de Toulouse, UPS, Service d’Hématologie, Toulouse, France
14Department of Medical Oncology, Cross Cancer Institute, University of Alberta and BC Cancer – Vancouver Centre Group, Alberta, Canada
15Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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, LLC, Spring House, PA
23Janssen Research & Development, Spring House, PA
24Janssen Research & Development, Raritan, NJ
25Memorial Sloan Kettering Cancer Center, New York, NY

Introduction: Daratumumab (DARA) is a human IgGκ monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action. DARA is approved as monotherapy and in combination with standard-of-care regimens for patients with relapsed/refractory multiple myeloma and in combination with standard-of-care regimens for patients with NDMM. In the primary analysis of the phase 3 MAIA study (median follow-up, 28.0 months), D-Rd significantly improved progression-free survival (PFS; median not reached [NR] vs 31.9 months; hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.43-0.73; P<0.001) and achieved a >3-fold increase in minimal residual disease (MRD)–negativity rate (10–5 sensitivity threshold; 24.2% vs 7.3%; P<0.001) versus Rd alone in transplant-ineligible patients with NDMM (Facon T, N Engl J Med 2019). With longer follow-up (median follow-up, 56.2 months), D-Rd significantly improved overall survival (OS) versus Rd (HR, 0.68; 95% CI, 0.53-0.86; P=0.0013; Facon T, Lancet Oncol 2021). Here, we present an updated analysis of MAIA after a median follow-up of 64.5 months.

Methods: Patients with NDMM ineligible for high-dose chemotherapy and autologous stem cell transplant were randomized 1:1 to receive Rd ± DARA. Randomization was stratified by International Staging System disease stage (I vs II vs III), region (North America vs other), and age (<75 vs ≥75 years). All patients received 28-day cycles of Rd (R: 25 mg PO on Days 1‑21; d: 40 mg PO on Days 1, 8, 15, and 22). In the D-Rd arm, DARA (16 mg/kg IV) was given once weekly in Cycles 1‑2, once every 2 weeks in Cycles 3-6, and once every 4 weeks thereafter. In both treatment arms, patients were treated until disease progression or unacceptable toxicity. The primary endpoint was PFS. Key secondary endpoints included MRD‑negativity rate (10–5 sensitivity, clonoSEQ® version 2.0), overall response rate (ORR), OS, and safety.

Results: In total, 737 patients were randomized (D-Rd, n=368; Rd, n=369). Baseline characteristics were well balanced between treatment arms. After a median follow-up of 64.5 months, PFS was improved with D-Rd versus Rd (median, 61.9 months vs 34.4 months; HR, 0.55; 95% CI, 0.45-0.67; P<0.0001; Figure A). A 34% reduction in the risk of death was observed with D-Rd versus Rd; median OS was NR with D-Rd versus 65.5 months with Rd (HR, 0.66; 95% CI, 0.53-0.83; P=0.0003). The estimated 60-month OS rate was 66.6% with D-Rd and 53.6% with Rd (Figure B). The ORR was higher for the D-Rd arm versus the Rd arm (92.9% vs 81.6%; P<0.0001). The MRD-negativity rate was also higher for D-Rd versus Rd (32.1% vs 11.1%; P<0.0001), as was the rate of sustained MRD negativity lasting ≥12 months (18.8% vs 4.1%; P<0.0001).

The most common (occurring in ≥15% of patients in either arm) grade 3/4 treatment-emergent adverse events (TEAEs; D-Rd/Rd) were neutropenia (54.1%/37.0%), anemia (17.0%/21.6%), pneumonia (19.5%/10.7%), and lymphopenia (16.5%/11.2%); grade 3/4 infection rates were 42.6%/29.6%. The most common serious TEAE in both arms was pneumonia (18.7%/10.7%). 14.6% of patients in the D-Rd arm and 23.8% of patients in the Rd arm discontinued treatment due to TEAEs.

Conclusions: In this updated analysis of MAIA, the addition of DARA to Rd continued to demonstrate PFS and OS benefits in transplant-ineligible patients with NDMM after a median follow-up of >5 years. D-Rd also achieved a nearly 3-fold higher MRD-negativity rate and a ≥4-fold higher ≥12-month sustained MRD-negativity rate versus Rd alone. No new safety concerns were observed with longer follow-up. These results continue to support the frontline use of D-Rd in transplant-ineligible patients with NDMM. Further updated OS results based on extended follow-up will be presented at the meeting.

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. Moreau: AbbVie, Amgen, Celgene, Janssen, Oncopeptides, Sanofi: Honoraria. Bahlis: Takeda: Consultancy; Forus: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Karyopharm Therapeutics: Consultancy, Honoraria; GSK: Consultancy, Other; Sanofi: Consultancy, Honoraria; Genentech: Consultancy; Amgen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding. Plesner: Janssen, Celgene, Takeda, Oncopeptides, Genentech, CSL Behring, AbbVie: Membership on an entity's Board of Directors or advisory committees; Janssen, Genmab, Celgene, Takeda, Oncopeptides, Genentech, AbbVie, Roche, Bristol Myers Squibb: Research Funding. Orlowski: 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; Asylia Therapeutics, Inc.: Current equity holder in private company; Asylia Therapeutics, Inc., BioTheryX, Inc., Heidelberg Pharma, Inc.: Research Funding; CARsgen Therapeutics, Celgene/Bristol Myers Squibb, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda Pharmaceuticals North America, Inc.: Research Funding. Basu: Sanofi, Pfizer, BMS: Consultancy, Speakers Bureau; Sanofi: Honoraria, Other: advisory board. Nahi: Genmab: Current Employment. Hulin: BMS: Honoraria; GSK: Honoraria; Takeda: Honoraria; Sanofi: Honoraria; Amgen: Honoraria; Janssen: Honoraria. Quach: AbbVie: Consultancy, Honoraria, 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; 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; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Antengene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, 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; CSL: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: leadership or fiduciary role , Research Funding; 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. Goldschmidt: Molecular Partners: Research Funding; Merck Sharp and Dohme (MSD): Research Funding; Mundipharma GmbH: 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; SANOFI: Consultancy, Honoraria, Other: Grants, Research Funding; Incyte: Research Funding; Celgene: Consultancy, Honoraria, Other: Grants, Research Funding; Janssen: Consultancy, Honoraria, Other: Grants, Research Funding; Chugai: Honoraria, Other: grants, Research Funding; BMS: Consultancy, Honoraria, Other: Grants, Research Funding; AMGEN: Consultancy, Honoraria, Other: Grants, 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; Array Biopharma: Research Funding; Dietmar-Hopp-Foundation: Research Funding. O'Dwyer: Janssen: Consultancy. Perrot: Pfizer: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: 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; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria; Sanofi: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Venner: Janssen, BMS, Sanofi, FORUS, Pfizer, GSK, Amgen: Honoraria. Weisel: Amgen: Consultancy, Honoraria, Research Funding; Novartis: Honoraria; BMS/Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria; Adaptive Biotech: Consultancy, Honoraria; AstraZeneca: Honoraria; BeiGene: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Oncopeptides: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Stemline: Honoraria; Pfizer: 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: Janssen: Honoraria, Other: Travel/accommodation, Research Funding; Takeda: Honoraria, Other: Travel/accommodation, Research Funding; GSK: Honoraria; Sanofi: Honoraria. Leleu: Amgen, Merck, BMS, GSK, Janssen, Oncopeptide, Takeda, Roche, Novartis, AbbVie, Sanofi, Gilead, Pfizer, Harpoon Therapeutic, Regeneron, Iteos: Consultancy, Honoraria; Pfizer: Honoraria; Amgen: Honoraria; Janssen: Honoraria; BMS: Honoraria; Takeda: Honoraria; Sanofi: 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. Krevvata: Janssen R& D, Johnson and Johnson: Current Employment. Carson: Janssen: Current Employment. Borgsten: Janssen: Current Employment. Usmani: Amgen, Array Biopharma, BMS, Celgene, GSK, Janssen Pharmaceuticals, Merck, Pharmacyclics, Sanofi, Seagen Inc., formerly Seattle Genetics, Inc., SkylineDX, Takeda: Consultancy; 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, BMS, Janssen Pharmaceuticals, Sanofi: Speakers Bureau.

*signifies non-member of ASH