Authors
Aurore Perrot, Salomon Manier, Cyrille Hulin, Hélène Demarquette, Arthur Bobin, Laurent Frenzel, Lionel Karlin, Olivier Decaux, Mohamad Mohty, Bertrand Arnulf, Jérôme Lambert, Jill Corre, Thierry Facon, Philippe Moreau, Cyrille Touzeau, Xavier Leleu, Intergroupe Francophone du Myélome (IFM)
Published in
Clinical lymphoma, myeloma & leukemia. Sep 09, 2026. Epub Sep 09, 2026.
Abstract
The treatment landscape of newly diagnosed multiple myeloma (NDMM) has changed considerably over the past 5 years. Anti-CD38-VRd quadruplets are now the standard of care for transplant-eligible patients and an important option for transplant-ineligible patients. This review presents unified, evidence-based first-line treatment recommendations from the Intergroupe Francophone du Myélome (IFM), covering transplant-eligible and transplant-ineligible NDMM within a single framework and common methodology. In transplant-eligible patients, daratumumab-VRd and isatuximab-VRd, informed respectively by the PERSEUS and GMMG-HD7 trials, are now the reference induction regimens, followed by autologous stem cell transplantation, optional consolidation, and daratumumab-lenalidomide maintenance. In transplant-ineligible patients, daratumumab-lenalidomide-dexamethasone (DRd), informed by the MAIA trial, remains the treatment backbone: in fit patients, adding bortezomib (isatuximab-VRd or daratumumab-VRd, informed by IMROZ, CEPHEUS, and BENEFIT) could further improve outcomes, while frail patients receive the same backbone without dexamethasone (DR), informed by IFM2017-03. Mathematical modeling projects a median progression-free survival of approximately 205 months with daratumumab-VRd in transplant-eligible patients (PERSEUS model) and approximately 100 months in transplant-ineligible/transplant-deferred patients (CEPHEUS model), approaching for the first time a normal life expectancy for a substantial subset of patients and supporting the emerging concept of functional cure. We discuss the role of measurable residual disease and NGS-based high-risk myeloma definition across both populations, and position these recommendations relative to the 2025 EHA-EMN evidence-based guidelines. Finally, we summarize ongoing trials investigating T-cell-redirecting immunotherapies (CAR-T cells and bispecific antibodies) as replacements for, or additions to, ASCT and maintenance therapy, which may further reshape the first-line treatment paradigm in the coming years.
PMID:
42888080
Bibliographic data and abstract were imported from PubMed on 17 Oct 2026.
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