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3245 Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) in Transplant-Ineligible Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM): Clinical Assessment of Key Subgroups of the Phase 3 Maia Study

Program: Oral and Poster Abstracts
Session: 653. Myeloma and Plasma Cell Dyscrasias: Prospective Therapeutic Trials: Poster II
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
Sunday, December 11, 2022, 6:00 PM-8:00 PM

Philippe Moreau, MD1*, Thierry Facon2*, Saad Usmani, MD3, Nizar Jacques Bahlis, MD4, Noopur Raje, MD5, Torben Plesner6, Robert Z. Orlowski, MD, PhD7, Supratik Basu8*, Hareth Nahi9*, Cyrille Hulin10*, Hang Quach11, Hartmut Goldschmidt, MD12, Michael O'Dwyer, MD13, Aurore Perrot, MD, PhD14*, Christopher P. Venner15,16*, Katja C. Weisel, MD17, Mourad Tiab18*, Margaret Macro, MD19*, Laurent Frenzel20*, Xavier Leleu, MD, PhD21, Huiling Pei, PhD22*, Maria Krevvata23*, Robin Carson23, Fredrik Borgsten24* and Shaji K Kumar, MD25

1Hematology Department, University Hospital Hôtel-Dieu, Nantes, France
2University of Lille, CHU Lille, Service des Maladies du Sang, Lille, France
3Memorial Sloan Kettering Cancer Center, New York, NY
4Arnie Charbonneau Cancer Research Institute, University of Calgary, Calgary, AB, Canada
5Center for Multiple Myeloma, Massachusetts General Hospital, Boston, MA
6Vejle Hospital and University of Southern Denmark, Vejle, Denmark
7Department of Lymphoma and Myeloma, MD Anderson Cancer Center, Houston, TX
8Royal Wolverhampton NHS Trust and University of Wolverhampton, CRN West Midlands, NIHR, Wolverhampton, United Kingdom
9Karolinska Institute, Department of Medicine, Division of Hematology, Karolinska University Hospital at Huddinge, Stockholm, Sweden
10Department of Hematology, Hôpital Haut Lévêque, University Hospital, Pessac, France
11University of Melbourne, St. Vincent’s Hospital, Melbourne, VIC, Australia
12University Hospital Heidelberg, Internal Medicine V and National Center for Tumor Diseases (NCT), Heidelberg, Germany
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, Edmonton, AB, Canada
16BC Cancer – Vancouver Centre Group, Vancouver, BC, Canada
17Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
18CHD Vendée, La Roche sur Yon, France
19Centre Hospitalier Universitaire (CHU) de Caen, Caen, France
20Hôpital Necker-Enfants Malades, Paris, France
21CHU Poitiers, Hôpital la Milétrie, Poitiers, France
22Janssen Research & Development, LLC, Titusville, NJ
23Janssen Research & Development, LLC, Spring House, PA
24Janssen Research & Development, LLC, Raritan, NJ
25Department of Hematology, Mayo Clinic Rochester, Rochester, MN

Introduction: The MAIA study (NCT02252172) evaluated D-Rd versus Rd alone in transplant-ineligible pts with NDMM. At a median follow-up of 56.2 months, D-Rd significantly improved progression-free survival (PFS) and overall survival versus Rd (Facon T, Lancet Oncol 2021). Here, we present an analysis of clinically important subgroups in MAIA, including pts aged ≥75 years, pts with International Staging System (ISS) stage III disease, pts with renal insufficiency (defined as baseline creatinine clearance [CrCl] ≤60 mL/min), pts with extramedullary plasmacytomas at baseline, and pts with high cytogenetic risk (defined as having ≥1 of the following high-risk cytogenetic abnormalities: t[4;14], t[14;16], del17p [per IMWG recommendations]).

Methods: In MAIA, pts with NDMM who were ineligible for high-dose chemotherapy and autologous stem-cell transplant were randomized 1:1 to receive D-Rd or Rd. All pts received 28-day cycles of oral Rd (R: 25 mg [10 mg recommended if CrCl was 30-50 mL/min] on Days 1-21; d: 40 mg [20 mg if aged >75 years or body-mass index <18.5 kg/m2] on Days 1, 8, 15, 22). Pts in the D-Rd arm received intravenous daratumumab (16 mg/kg QW in Cycles 1-2, Q2W in Cycles 3-6, and Q4W thereafter). Pts in both arms were treated until disease progression or unacceptable toxicity. The primary endpoint was PFS, and key secondary endpoints included overall response rate (ORR) and minimal residual disease (MRD)–negativity rate (10–5 sensitivity).

Results: 737 pts were randomized (D-Rd, n=368; Rd, n=369); most subgroups had a similar number of pts per treatment arm: age ≥75 years (n=160; n=161); ISS stage III (n=107; n=110); renal insufficiency (n=162; n=142); extramedullary plasmacytomas (n=15; n=9); and high cytogenetic risk (n=48; n=44). After a 64.5-month median follow-up, PFS (Figure A) and ORR (Figure B) generally favored D-Rd versus Rd across subgroups. MRD-negativity rates were higher with D-Rd versus Rd for pts aged ≥75 years (26.9% vs 9.9%; P<0.0001), pts with ISS stage III disease (27.1% vs 10.9%; P=0.0030), pts with renal insufficiency (29.6% vs 7.7%; P<0.0001), pts with extramedullary plasmacytomas (33.3% vs 0%; P=0.1181), and pts with high cytogenetic risk (25.0% vs 2.3%; P=0.0019). Sustained (≥6 months and ≥12 months) MRD-negativity rates were higher with D-Rd versus Rd across subgroups: age ≥75 years (≥6 months, 15.6% vs 5.0%; ≥12 months, 13.8% vs 3.1%), ISS stage III disease (≥6 months, 17.8% vs 3.6%; ≥12 months, 15.9% vs 2.7%), renal insufficiency (≥6 months, 21.0% vs 1.4%; ≥12 months, 18.5% vs 1.4%), extramedullary plasmacytomas (≥6 months, 26.7% vs 0%; ≥12 months, 13.3% vs 0%), and high cytogenetic risk (≥6 months, 12.5% vs 0%; ≥12 months, 12.5% vs 0%).

In an analysis of safety among pts aged ≥75 years, grade 3/4 treatment-emergent adverse events (TEAEs) occurred in 95.5% of D-Rd pts and 95.0% of Rd pts; the most common (≥20%; D-Rd/Rd) were neutropenia (62.4%/41.5%), lymphopenia (21.0%/12.6%), anemia (20.4%/25.2%), and pneumonia (20.4%/14.5%). Serious TEAEs occurred in 80.9% and 79.2% of D-Rd and Rd pts, respectively. TEAEs led to study treatment discontinuation in 15.3% of D-Rd pts and 27.7% of Rd pts. TEAEs with an outcome of death occurred in 11.5% of D-Rd pts and 13.2% Rd pts.

Conclusions: In this subgroup analysis of MAIA, D-Rd improved PFS, ORR, and MRD-negativity rates versus Rd across clinically important subgroups, including pts aged ≥75 years, pts with ISS stage III disease, pts with renal insufficiency, pts with extramedullary plasmacytomas, and pts with high cytogenetic risk. In pts aged ≥75 years, the rates of grade 3/4 and serious TEAEs were similar with D-Rd and Rd, with a lower rate of discontinuation due to TEAEs for D-Rd versus Rd. Results for these clinically important subgroups provide confidence in using D-Rd across all pt types, supporting D-Rd as a standard of care for transplant-ineligible pts with NDMM. Results for additional cytogenetic risk subgroups that include pts with gain and/or amp 1q21 will be presented at the meeting.

Disclosures: Moreau: AbbVie, Amgen, Celgene, Janssen, Oncopeptides, Sanofi: 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. Bahlis: Pfizer: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Genentech: Consultancy; Karyopharm Therapeutics: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Forus: Consultancy, Honoraria; GSK: Consultancy, Other; Takeda: Consultancy. 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. 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., 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; Asylia Therapeutics, Inc.: Current equity holder in private company. 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: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, 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; 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; 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; Antengene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, 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: 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; Incyte: Research Funding; 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; Amgen, BMS, Chugai, GlaxoSmithKline, Janssen, Novartis, Sanofi, Pfizer: Honoraria; AMGEN: Consultancy, Honoraria, Other: Grants, Research Funding; Amgen, BMS, GlaxoSmithKline, Janssen, Novartis, Sanofi, Pfizer: Other: Support for attending meetings and/or travel; Array Biopharma: Research Funding; Celgene: Consultancy, Honoraria, Other: Grants, 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. Macro: Janssen: Honoraria, Other: Travel/accommodation, Research Funding; Sanofi: Honoraria; GSK: Honoraria; Takeda: Honoraria, Other: Travel/accommodation, Research Funding. Leleu: Janssen: Honoraria; Takeda: Honoraria; Amgen, BMS/Celgene, Janssen, Takeda, Novartis, Sanofi, Merck, Oncopeptide, Karyopharm, Roche, Abbvie, Carsgen, GSK, and Harpoon Therapeutics: Honoraria; Amgen: Honoraria; Amgen, Merck, BMS, GSK, Janssen, Oncopeptide, Takeda, Roche, Novartis, AbbVie, Sanofi, Gilead, Pfizer, Harpoon Therapeutic, Regeneron, Iteos: Consultancy, Honoraria; BMS: Honoraria; Pfizer: Honoraria; Sanofi: 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. 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.

*signifies non-member of ASH