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Clinical Trial
. 2025 Apr;39(4):942-950.
doi: 10.1038/s41375-024-02505-2. Epub 2025 Feb 27.

Daratumumab/lenalidomide/dexamethasone in transplant-ineligible newly diagnosed myeloma: MAIA long-term outcomes

Thierry Facon  1 , Philippe Moreau  2 , Katja Weisel  3 , Hartmut Goldschmidt  4 , Saad Z Usmani  5 , Ajai Chari  6 , Torben Plesner  7 , Robert Z Orlowski  8 , Nizar Bahlis  9 , Supratik Basu  10 , Cyrille Hulin  11 , Hang Quach  12 , Michael O'Dwyer  13 , Aurore Perrot  14 , Caroline Jacquet  15 , Christopher P Venner  16   17 , Noopur Raje  18 , Mourad Tiab  19 , Margaret Macro  20 , Laurent Frenzel  21 , Xavier Leleu  22 , Gordon Cook  23 , George Wang  24 , Huiling Pei  25 , Maria Krevvata  24 , Robin Carson  24 , Fredrik Borgsten  26 , Shaji K Kumar  27
Affiliations
Clinical Trial

Daratumumab/lenalidomide/dexamethasone in transplant-ineligible newly diagnosed myeloma: MAIA long-term outcomes

Thierry Facon et al. Leukemia. 2025 Apr.

Abstract

In the MAIA study, daratumumab plus lenalidomide and dexamethasone (D-Rd) improved progression-free survival (PFS) and overall survival (OS) versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). We report updated efficacy and safety from MAIA (median follow-up, 64.5 months), including a subgroup analysis by patient age (<70, ≥70 to <75, ≥75, and ≥80 years). Overall, 737 transplant-ineligible patients with NDMM were randomized 1:1 to D-Rd or Rd. The primary endpoint, PFS, was improved with D-Rd versus Rd (median, 61.9 vs 34.4 months; hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.45-0.67; P < 0.0001). Median OS was not reached in the D-Rd group versus 65.5 months in the Rd group (HR, 0.66; 95% CI, 0.53-0.83; P = 0.0003); estimated 60-month OS rates were 66.6% and 53.6%, respectively. D-Rd achieved higher rates of complete response or better (≥CR; 51.1% vs 30.1%), minimal residual disease (MRD) negativity (32.1% vs 11.1%), and sustained MRD negativity (≥18 months: 16.8% vs 3.3%) versus Rd (all P < 0.0001). D-Rd demonstrated clinically meaningful efficacy benefits across age groups. No new safety concerns were observed. Updated results (median follow-up, >5 years) continue to support frontline use of D-Rd in transplant-ineligible patients with NDMM.

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Conflict of interest statement

Competing interests: TF has nothing to disclose. PM served on an advisory board for and received honoraria from Janssen, Celgene, Amgen, AbbVie, Sanofi, and Oncopeptides. KW received research funding from Amgen, Adaptive Biotechnologies, AstraZeneca, Bristol Myers Squibb/Celgene, BeiGene, Janssen, GSK, Sanofi, Stemline, and Takeda; received honoraria from AbbVie, Amgen, Adaptive Biotechnologies, AstraZeneca, Bristol Myers Squibb/Celgene, BeiGene, Janssen, GSK, Karyopharm, Novartis, Oncopeptides, Pfizer, Roche, Sanofi, Stemline, and Takeda; and received travel support from Janssen, GSK, and Sanofi. HG received grants and/or provisions of Investigational Medicinal Product from Amgen, Array BioPharma/Pfizer, Bristol Myers Squibb/Celgene, Chugai, Dietmar Hopp Foundation, Janssen, Johns Hopkins University, Mundipharma, and Sanofi; received research support from Amgen, Bristol Myers Squibb, Celgene, GlycoMimetics, GSK, Heidelberg Pharma, Roche, Karyopharm, Janssen, Incyte, Millennium Pharmaceuticals, Molecular Partners, Merck Sharp & Dohme, MorphoSys AG, Pfizer, Sanofi, Takeda, and Novartis; served on an advisory board for Amgen, Bristol Myers Squibb, Janssen, Sanofi, and Adaptive Biotechnologies; received honoraria from Amgen, Bristol Myers Squibb, Chugai, GSK, Janssen, Novartis, Sanofi, and Pfizer; and received support for attending meetings and/or travel from Amgen, Bristol Myers Squibb, GSK, Janssen, Novartis, Sanofi, and Pfizer. SZU received research funding from Amgen, Array BioPharma, Bristol Myers Squibb, Celgene, GSK, Janssen, Merck, Pharmacyclics, Sanofi, Seattle Genetics, SkylineDx, and Takeda; served in a consulting role for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Edo Pharma, Genentech, Gilead, GSK, Janssen, Oncopeptides, Sanofi, Seattle Genetics, Secura Bio, SkylineDx, Takeda, and TeneoBio; and served on a speakers bureau for Amgen, Bristol Myers Squibb, Janssen, and Sanofi. AC served in a consulting role or on an advisory board for AbbVie, Amgen, Antengene, Celgene/Bristol Myers Squibb, Janssen, Karyopharm, GSK, Genentech, Sanofi, Seattle Genetics, Secura Bio, Shattuck Labs, and Millennium/Takeda; and received research funding from Amgen, Celgene/Bristol Myers Squibb, Janssen, Seattle Genetics, and Millennium/Takeda. TP served as an advisor for Janssen, Celgene, Takeda, Oncopeptides, Genentech, CSL Behring, and AbbVie; and received research support from Janssen, Genmab, Celgene, Takeda, Oncopeptides, Genentech, AbbVie, and Roche. RZO received research funding from Asylia Therapeutics, Biotheryx, Heidelberg Pharma, CARsgen, Celgene/Bristol Myers Squibb, Exelixis, Janssen, Sanofi-Aventis, and Takeda; received honoraria from and served as a member on a board of directors or advisory committee for AbbVie, Biotheryx, Bristol Myers Squibb, Janssen, Karyopharm, Meridian Therapeutics, Monte Rosa Therapeutics, Neoleukin, Oncopeptides, Regeneron, Sanofi-Aventis, and Takeda; and holds stock in Asylia Therapeutics. NB served in a consulting or advisory role for and received honoraria from AbbVie, Bristol Myers Squibb/Celgene, FORUS, Genentech, Janssen, Karyopharm, Pfizer, Sanofi, and Takeda; and received research funding from Pfizer and Celgene. SB served as a consultant and on a speakers bureau for Sanofi, Pfizer, and Bristol Myers Squibb. CH received honoraria from Janssen, Bristol Myers Squibb, Amgen, Takeda, and AbbVie. HQ served as a consultant for and received research funding from AbbVie, Bristol Myers Squibb, Karyopharm, Amgen, GSK, and Antengene. MO served as a consultant for Janssen. AP received honoraria from AbbVie, Amgen, Celgene/Bristol Myers Squibb, GSK, Janssen, Sanofi, and Takeda; served as a member on a board or advisory committee for Amgen, Celgene/Bristol Myers Squibb, GSK, Janssen, Pfizer, and Takeda; and received research funding from Takeda. CJ served as a member on a board or advisory committee for Amgen and GSK. CPV received honoraria from Janssen, Bristol Myers Squibb, Sanofi, FORUS, Pfizer, AbbVie, GSK, and Amgen. NR served as a consultant for Bristol Myers Squibb, Janssen, Takeda, Amgen, and GSK; and received research funding from bluebird bio. MT has nothing to disclose. MM served on an advisory board for Celgene/Bristol Myers Squibb, Janssen, Takeda, Amgen, GSK, and Sanofi; received research funding from Janssen and Takeda; and received accommodations from Janssen, Celgene/Bristol Myers Squibb, Takeda, Amgen, and Sanofi. LF received honoraria from Janssen, Sanofi, Amgen, and Takeda; and received funding from Janssen and Amgen. XL received honoraria, research support, and consulting fees from Amgen, Merck, Bristol Myers Squibb, GSK, Janssen, Oncopeptides, Takeda, Roche, Novartis, AbbVie, Sanofi, Gilead, Pfizer, Harpoon Therapeutics, Regeneron, and iTeos. GC received research support from Bristol Myers Squibb/Celgene, Janssen, and Takeda; and served as a consultant for and received honoraria from Amgen, Bristol Myers Squibb/Celgene, Janssen, Millennium/Takeda, Roche, GSK, Oncopeptides, and Sanofi. GW, HP, and FB are employees of Janssen and hold stock in Johnson & Johnson. MK and RC are employees of Janssen. SKK has received research funding from AbbVie, Amgen, Allogene, AstraZeneca, Bristol Myers Squibb, CARsgen, GSK, Janssen, Novartis, Roche-Genentech, Takeda, Regeneron, and Molecular Templates; participated in consulting or an advisory board (with no personal payments) for AbbVie, Amgen, Bristol Myers Squibb, Janssen, Roche-Genentech, Takeda, AstraZeneca, bluebird bio, Epizyme, Secura Bio, Monte Rosa Therapeutics, Trillium, Loxo Oncology, K36, Sanofi, and Arcellx; and participated in consulting or an advisory board (with personal payments) for Oncopeptides, BeiGene, Antengene, and GLH Pharma.

Figures

Fig. 1
Fig. 1. PFS and OS in the ITT population.
Kaplan–Meier estimates of (A) PFS and (B) OS in the ITT population. PFS progression-free survival, OS overall survival, ITT intent-to-treat, D-Rd daratumumab plus lenalidomide/dexamethasone, Rd lenalidomide/dexamethasone, HR hazard ratio, CI confidence interval, NR not reached.
Fig. 2
Fig. 2. PFS and OS by age subgroup.
Kaplan–Meier estimates of (A) PFS in patients aged <70 years, ≥70 to <75 years, and ≥75 years; (B) PFS in patients aged ≥80 years; (C) OS in patients aged <70 years, ≥70 to <75 years, and ≥75 years; and (D) OS in patients aged ≥80 years. PFS progression-free survival, OS overall survival, D-Rd daratumumab plus lenalidomide/dexamethasone, Rd lenalidomide/dexamethasone, HR hazard ratio, CI confidence interval, NR not reached.
Fig. 3
Fig. 3. Cumulative best response rates of ≥CR and MRD negativity over time in the ITT population.
A Cumulative ≥CR and (B) MRD-negativity rates by 12, 18, 24, 30, 36, 48, and 60 months in the ITT population. CR complete response, MRD minimal residual disease, ITT intent-to-treat, D-Rd daratumumab plus lenalidomide/dexamethasone, Rd lenalidomide/dexamethasone.
Fig. 4
Fig. 4. Response rates over time in the ITT population.
Response rates by 6, 12, 18, 24, and 30 months in the ITT population. ITT intent-to-treat, ORR overall response rate, CR complete response, D-Rd daratumumab plus lenalidomide/dexamethasone, Rd lenalidomide/dexamethasone, PR partial response, VGPR very good partial response, sCR stringent complete response.
See this image and copyright information in PMC

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