Isatuximab, carfilzomib, lenalidomide, and dexamethasone induction in newly diagnosed myeloma: analysis of the MIDAS trial

ABSTRACT: For patients with transplant-eligible newly diagnosed multiple myeloma, induction therapy with a quadruplet regimen before autologous transplant is the standard of care. The phase 3 IFM2020-02-MRD-adapted strategy (MIDAS) study assessed a minimal residual disease (MRD)-driven consolidation and maintenance strategy after induction with isatuximab, carfilzomib, lenalidomide, and dexamethasone (IsaKRD). We report safety and efficacy outcomes of six 28-day cycles of IsaKRD in 791 patients. The median age was 59 years; 13% had International Staging System (ISS) stage III, 5% Revised-ISS stage III, and 8% high-risk cytogenetics (Intergroupe Francophone du Myélome linear predictor cytogenetic score of >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. 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. This trial was registered at www.clinicaltrials.gov as #NCT04934475.