Daratumumab plus lenalidomide/dexamethasone in untreated multiple myeloma: analysis of key subgroups of the MAIA study

Philippe Moreau¹, Thierry Facon², Saad Z Usmani³, Nizar Bahlis⁴, Noopur Raje⁵, Torben Plesner⁶, Robert Z Orlowski⁷, Supratik Basu⁸, Hareth Nahi⁹, Cyrille Hulin¹⁰, Hang Quach¹¹, Hartmut Goldschmidt¹², Michael O'Dwyer¹³, Aurore Perrot¹⁴, Christopher P Venner^{15

16}, Katja Weisel¹⁷, Mourad Tiab¹⁸, Margaret Macro¹⁹, Laurent Frenzel²⁰, Xavier Leleu²¹, George Wang²², Huiling Pei²³, Maria Krevvata²², Robin Carson²², Fredrik Borgsten²⁴, Shaji K Kumar²⁵

Affiliations

¹ Hematology Department, University Hospital Hôtel-Dieu, Nantes, France. philippe.moreau@chu-nantes.fr.
² University of Lille, CHU Lille, Service des Maladies du Sang, Lille, France.
³ Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁴ Arnie Charbonneau Cancer Research Institute, University of Calgary, Calgary, AB, Canada.
⁵ Center for Multiple Myeloma, Massachusetts General Hospital Cancer Center, Boston, MA, USA.
⁶ Vejle Hospital and University of Southern Denmark, Vejle, Denmark.
⁷ Department of Lymphoma & Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁸ Royal Wolverhampton NHS Trust and University of Wolverhampton, CRN West Midlands, NIHR, Wolverhampton, UK.
⁹ Karolinska Institute, Department of Medicine, Division of Hematology, Karolinska University Hospital at Huddinge, Stockholm, Sweden.
¹⁰ Department of Hematology, Hôpital Haut Lévêque, University Hospital, Pessac, France.
¹¹ University of Melbourne, St Vincent's Hospital, Melbourne, Australia.
¹² GMMG-Study Group at University Hospital Heidelberg, Internal Medicine V, Heidelberg, Germany.
¹³ Department of Medicine/Haematology, University of Galway, Galway, Republic of Ireland.
¹⁴ CHU de Toulouse, IUCT-O, Université de Toulouse, UPS, Service d'Hématologie, Toulouse, France.
¹⁵ Department of Medical Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada.
¹⁶ Department of Medical Oncology, BC Cancer - Vancouver Centre, University of British Columbia, Vancouver, BC, Canada.
¹⁷ Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹⁸ CHD Vendée, La Roche sur Yon, France.
¹⁹ Centre Hospitalier Universitaire (CHU) de Caen, Caen, France.
²⁰ Hôpital Necker-Enfants Malades, Paris, France.
²¹ CHU Poitiers, Hôpital la Milétrie, Poitiers, France.
²² Janssen Research & Development, LLC, Spring House, PA, USA.
²³ Janssen Research & Development, LLC, Titusville, NJ, USA.
²⁴ Janssen Research & Development, LLC, Raritan, NJ, USA.
²⁵ Department of Hematology, Mayo Clinic Rochester, Rochester, MN, USA.

PMID: 39815052
DOI: 10.1038/s41375-024-02506-1

Clinical Trial

Daratumumab plus lenalidomide/dexamethasone in untreated multiple myeloma: analysis of key subgroups of the MAIA study

Philippe Moreau et al. Leukemia. 2025 Mar.

. 2025 Mar;39(3):710-719.

doi: 10.1038/s41375-024-02506-1. Epub 2025 Jan 15.

Authors

Affiliations

¹ Hematology Department, University Hospital Hôtel-Dieu, Nantes, France. philippe.moreau@chu-nantes.fr.
² University of Lille, CHU Lille, Service des Maladies du Sang, Lille, France.
³ Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁴ Arnie Charbonneau Cancer Research Institute, University of Calgary, Calgary, AB, Canada.
⁵ Center for Multiple Myeloma, Massachusetts General Hospital Cancer Center, Boston, MA, USA.
⁶ Vejle Hospital and University of Southern Denmark, Vejle, Denmark.
⁷ Department of Lymphoma & Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁸ Royal Wolverhampton NHS Trust and University of Wolverhampton, CRN West Midlands, NIHR, Wolverhampton, UK.
⁹ Karolinska Institute, Department of Medicine, Division of Hematology, Karolinska University Hospital at Huddinge, Stockholm, Sweden.
¹⁰ Department of Hematology, Hôpital Haut Lévêque, University Hospital, Pessac, France.
¹¹ University of Melbourne, St Vincent's Hospital, Melbourne, Australia.
¹² GMMG-Study Group at University Hospital Heidelberg, Internal Medicine V, Heidelberg, Germany.
¹³ Department of Medicine/Haematology, University of Galway, Galway, Republic of Ireland.
¹⁴ CHU de Toulouse, IUCT-O, Université de Toulouse, UPS, Service d'Hématologie, Toulouse, France.
¹⁵ Department of Medical Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada.
¹⁶ Department of Medical Oncology, BC Cancer - Vancouver Centre, University of British Columbia, Vancouver, BC, Canada.
¹⁷ Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹⁸ CHD Vendée, La Roche sur Yon, France.
¹⁹ Centre Hospitalier Universitaire (CHU) de Caen, Caen, France.
²⁰ Hôpital Necker-Enfants Malades, Paris, France.
²¹ CHU Poitiers, Hôpital la Milétrie, Poitiers, France.
²² Janssen Research & Development, LLC, Spring House, PA, USA.
²³ Janssen Research & Development, LLC, Titusville, NJ, USA.
²⁴ Janssen Research & Development, LLC, Raritan, NJ, USA.
²⁵ Department of Hematology, Mayo Clinic Rochester, Rochester, MN, USA.

PMID: 39815052
DOI: 10.1038/s41375-024-02506-1

Abstract

In the MAIA study (median follow-up, 56.2 months), daratumumab plus lenalidomide and dexamethasone (D-Rd) significantly improved progression-free survival (PFS) and overall survival versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible newly diagnosed multiple myeloma (NDMM). In this post hoc analysis of clinically important subgroups in MAIA (median follow-up, 64.5 months), transplant-ineligible patients with NDMM were randomized 1:1 to D-Rd or Rd. The primary endpoint was PFS; secondary endpoints included overall response rate (ORR) and measurable residual disease (MRD)-negativity rate (10^-5). PFS favored D-Rd versus Rd in most subgroups, including patients aged ≥75 years (HR, 0.59; 95% CI, 0.44-0.79), frail patients (HR, 0.64; 95% CI, 0.48-0.85), patients with high-risk cytogenetics (HR, 0.59; 95% CI, 0.44-0.80), and patients with isolated gain(1q21) (HR, 0.36; 95% CI, 0.19-0.67). ORRs, MRD-negativity rates, and sustained (≥12 months) MRD-negativity rates were higher with D-Rd versus Rd across subgroups. In patients aged ≥75 years, rates of grade 3/4 and serious treatment-emergent adverse events (TEAEs) were similar for D-Rd and Rd, but discontinuation due to TEAEs was lower for D-Rd. Results support use of D-Rd for high-risk patients, supporting D-Rd as a standard of care for transplant-ineligible NDMM. This trial was registered at www.clinicaltrials.gov as NCT02252172.

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Conflict of interest statement

Competing interests: PM served on an advisory board for and received honoraria from Janssen, Celgene, Amgen, AbbVie, Sanofi, and Oncopeptides. TF has nothing to disclose. SZU received research funding from Amgen, Array BioPharma, Bristol Myers Squibb, Celgene, GlaxoSmithKline, 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, GlaxoSmithKline, 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. 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. NR served as a consultant for Bristol Myers Squibb, Janssen, Takeda, Amgen, and GlaxoSmithKline; and received research funding from bluebird bio. 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. SB served as a consultant and on a speakers bureau for Sanofi, Pfizer, and Bristol Myers Squibb. HN is an employee of Genmab. 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, GlaxoSmithKline, and Antengene. 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, GlaxoSmithKline, 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, GlaxoSmithKline, Janssen, Novartis, Sanofi, and Pfizer; and received support for attending meetings and/or travel from Amgen, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Novartis, Sanofi, and Pfizer. MO served as a consultant for Janssen. AP received honoraria from AbbVie, Amgen, Celgene/Bristol Myers Squibb, GlaxoSmithKline, Janssen, Sanofi, and Takeda; served as a member on a board or advisory committee for Amgen, Celgene/Bristol Myers Squibb, GlaxoSmithKline, Janssen, Pfizer, and Takeda; and received research funding from Takeda. CPV received honoraria from Janssen, Bristol Myers Squibb, Sanofi, FORUS, Pfizer, AbbVie, GlaxoSmithKline, and Amgen. KW received research funding from Amgen, Adaptive Biotechnologies, AstraZeneca, Bristol Myers Squibb/Celgene, BeiGene, Janssen, GlaxoSmithKline, Sanofi, Stemline, and Takeda; received honoraria from AbbVie, Amgen, Adaptive Biotechnologies, AstraZeneca, Bristol Myers Squibb/Celgene, BeiGene, Janssen, GlaxoSmithKline, Karyopharm, Novartis, Oncopeptides, Pfizer, Roche, Sanofi, Stemline, and Takeda; and received travel support from Janssen, GlaxoSmithKline, and Sanofi. MT has nothing to disclose. MM served on an advisory board for Celgene/Bristol Myers Squibb, Janssen, Takeda, Amgen, GlaxoSmithKline, 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, GlaxoSmithKline, Janssen, Oncopeptides, Takeda, Roche, Novartis, AbbVie, Sanofi, Gilead, Pfizer, Harpoon Therapeutics, Regeneron, and iTeos. GW, HP, and FB are employees of Janssen and hold stock in Johnson & Johnson. MK and RC are employees of Janssen. SKK received research funding from AbbVie, Amgen, Allogene, AstraZeneca, Bristol Myers Squibb, CARsgen, GlaxoSmithKline, 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.

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Daratumumab plus lenalidomide/dexamethasone in untreated multiple myeloma: analysis of key subgroups of the MAIA study

Affiliations

Daratumumab plus lenalidomide/dexamethasone in untreated multiple myeloma: analysis of key subgroups of the MAIA study

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

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Associated data

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Full Text Sources

Medical

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