In a French-Belgian phase III trial (MIDAS) reported at the 2025 ASCO Annual Meeting and in The New England Journal of Medicine, Perrot et al examined the outcomes of treatments guided by measurable residual disease (MRD) status in patients with newly diagnosed multiple myeloma.
Study Details
In the open-label multicenter trial, 718 transplant-eligible patients who had completed induction with isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) were randomly assigned to treatment between December 2021 and July 2023 according to MRD status. Patients who were MRD-negative at 10-5 sensitivity (n = 485) were assigned to undergo autologous stem-cell transplantation (ASCT) and receive Isa-KRd for two cycles (ASCT group; n = 242) or to receive Isa-KRd for six cycles (Isa-KRd group; n = 243). Patients who were MRD-positive at 10-5 sensitivity (n = 233) were assigned to receive tandem ASCT (n = 124) or ASCT and Isa-KRd for three cycles (n = 109). The primary outcome measure was MRD-negative status at 10-6 sensitivity prior to maintenance therapy.
Key Points
Among 485 patients who were MRD-negative at 10-5 sensitivity after induction, premaintenance MRD-negative status at 10-6 sensitivity was observed in 86% of the ASCT group vs 84% of the Isa-KRd group (adjusted relative risk [RR] = 1.02, 95% confidence interval [CI] = 0.95–1.10, P = .64).
Among 233 patients who were MRD-positive at 10-5 sensitivity after induction, premaintenance MRD-negative status at 10-6 sensitivity was observed in 32% of the tandem ASCT group vs 40% of the single ASCT group (adjusted RR = 0.82, 95% CI = 0.58–1.15, P = .31); a total of 15% of patients in the tandem ASCT group did not undergo a second ASCT.
Serious adverse events occurred in 15% of the ASCT and Isa-KRd groups and in 19% of the tandem ASCT and single ASCT groups. According to investigators, no new safety signals were observed.
The investigators concluded: “Among patients who were MRD-negative at 10-5 sensitivity after induction, the percentage with a premaintenance MRD-negative status at 10-6 sensitivity was not significantly higher with ASCT than with Isa-KRd. Among patients who were MRD-positive status at 10-5 sensitivity after induction, the percentage with a premaintenance MRD-negative status at 10-6 sensitivity was not significantly higher with tandem ASCT than with single ASCT.”
Aurore Perrot, MD, of Service Hematologie, Hopital Universitaire de Toulouse Oncopole, Universite de Toulouse, Toulouse, France is the corresponding author for the New England Journal of Medicine article.
Disclosure: The study was funded by Intergroupe Francophone du Myelome and others. For full disclosures of all study authors, visit nejm.org.
