Isatuximab, carfilzomib, lenalidomide and dexamethasone in newly diagnosed multiple myeloma: a randomized phase 3 trial
Mené sur 302 patients atteints d'un myélome multiple récemment diagnostiqué, cet essai randomisé de phase III évalue l'efficacité, du point de vue du taux de maladie résiduelle, et la toxicité d'un traitement combinant isatuximab, carfilzomib, lénalidomide et dexaméthasone en traitement d'induction puis en consolidation après une greffe autologue de cellules souches hématopoïétiques
Induction and consolidation with a quadruplet therapy of a CD38-targeting monoclonal antibody, a proteasome inhibitor, an immunomodulatory drug and dexamethasone are a standard-of-care treatment in transplant-eligible (TE) patients with newly diagnosed multiple myeloma (NDMM) with the optimal drugs to be used still under debate. The ongoing, phase 3 EMN24 IsKia trial randomized 302 TE patients with NDMM aged ≤70 years 1:1 to isatuximab–carfilzomib–lenalidomide–dexamethasone (Isa-KRd) versus KRd pretransplant induction and post-transplant consolidation. The primary endpoint was the rate of measurable residual disease (MRD) negativity (sensitivity of 10−5 or better) by next-generation sequencing (NGS) after consolidation. Key secondary endpoints were the rates of NGS-MRD negativity after induction and progression-free survival (PFS). MRD negativity rates at higher sensitivity (10−6 or better) were exploratory. Post-consolidation MRD negativity was significantly higher with Isa-KRd versus KRd at the 10−5 (77% versus 67%; odds ratio (OR) 1.67, P = 0.049) and 10−6 (68% versus 48%; OR 2.36, P = 0.0004) sensitivities. Deep MRD responses were rapid (post-induction Isa-KRd versus KRd: 10−5 46% versus 27%, OR 2.32, P = 0.0007; 10−6 28% versus 14%, OR 2.44, P = 0.0029) and durable (1-year sustained 10−6 MRD negativity 52% versus 38%, OR 1.82, P = 0.012). At current follow-up, PFS data were immature. Grade 3–4 non-hematologic adverse events (AEs), treatment discontinuations and deaths due to AEs were similar in the two arms. Isa-KRd significantly improved NGS-MRD negativity in TE patients with NDMM, with a manageable safety profile. ClinicalTrials.gov registration: NCT04483739.
Nature Medicine , article en libre accès, 2026