Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone Induction in Newly Diagnosed Myeloma: Analysis of the MIDAS Trial
Mené sur 791 patients atteints d'un myélome multiple (âge médian : 59 ans), cet essai de phase III évalue l'efficacité, du point de vue du taux de réponse globale et du taux d'absence de maladie résiduelle minimale, et la toxicité d'un traitement d'induction par isatuximab, carfilzomib, lénalidomide et dexaméthasone
Résumé en anglais
In patients with transplant-eligible newly diagnosed multiple myeloma, induction therapy with a quadruplet regimen prior to autologous transplant is the standard of care. The phase III IFM2020-02-MIDAS study (NCT04934475) assessed a minimal residual disease (MRD)-driven consolidation and maintenance strategy following induction with isatuximab, carfilzomib, lenalidomide, and dexamethasone (IsaKRD). Here, we report safety and efficacy outcomes of six 28-day cycles of IsaKRD. Between December 2021 and July 2023, 791 patients were enrolled across 72 centers. The median age was 59 years; 13% had ISS-stage III, 5% had R-ISS-stage III, and 8% had high-risk cytogenetics (IFM Linear Predictor cytogenetic score >1). Overall, 96% (N=757) of patients completed induction. The median CD34+ cell yield was 7 × 106/Kg, with 94% of patients able to proceed with a potential tandem transplant. The best overall response rate was 95%. In the intent-to-treat population, 91% achieved a very good partial response or better after induction, with MRD-negativity rates of 63% at 10-5 and 47% at 10-6. MRD-negativity rates differed across ISS stages and cytogenetic subgroups. During induction, 7 patients experienced disease progression, and 5 died due to disease progression (N=1), cardiac events (N=2), or other causes (N=2). The most common grade 3/4 adverse events were neutropenia (25%), thrombocytopenia (5%), and infections (7%); only 13% of patients reported any grade peripheral neuropathy. IsaKRD induction yielded deep responses and high MRD-negativity rates while ensuring successful stem cell collection, with no new safety signals. Continued follow-up of this ongoing study is required to confirm these findings.
