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
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.
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