The MIDAS trial: MRD guided therapy for newly-diagnosed multiple myeloma

The phase III IFM2020-02-MIDAS study is evaluating a minimal residual disease (MRD)-driven consolidation and maintenance treatment strategy following induction with isatuximab, carfilzomib, lenalidomide, and dexamethasone (IsaKRD) in transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). Earlier this year, results of the induction phase of this study showed that Isa-KRD leads to deep responses and rates of high MRD-negativity. At EHA 2025, early results of the MRD-driven consolidation phase of the trial were presented. In this video, Prof Claudio Cerchione, hematologist at the Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori in Meldola (Italy) explains why MRD-driven treatment strategies like the one evaluated in MIDAS is the way to go in the future management of MM.

The MIDAS trial randomly assigned transplantation-eligible NDMM patients who had completed induction therapy with Isa-KRd to receive consolidation therapy according to their MRD status. Patients who were MRD-negative at a sensitivity of 10⁻⁵ by next-generation sequencing (NGS) were randomly assigned to undergo an autologous stem cell transplantation (ASCT) followed by 2 cycles of Isa-KRd (ASCT group) or to receive Isa-KRd for six cycles (Isa-KRd group). In contrast, patients who were MRD-positive at 10⁻⁵ sensitivity were randomized between a tandem ASCT or an ASCT followed by Isa-KRd for two cycles (single ASCT group). The primary endpoint was an MRD-negative status at 10⁻⁶ sensitivity before maintenance therapy.

Among patients who were MRD-negative after induction (N= 485), an ASCT did not increase the MRD-negativity (10⁻⁶) rate prior to maintenance therapy (86% in the ASCT group vs. 84% in the Isa-KRd arm). As such, these data suggest that an ASCT does not offer additional benefit in this highly responsive patient subset after induction with a potent quadruplet regimen. Among patients who were MRD-positive after induction (N= 233), 32% achieved MRD negativity (10⁻⁶) prior to maintenance therapy if they received a tandem ASCT as compared to 40% if they received a single ASCT followed by 2 cycles of Isa-KRd. As such, these findings question the role of a tandem ASCT in the current era of quadruplet regimens. However, longer follow-up will be necessary to evaluate the durability of the MRD negativity that was obtained in this trial and to assess the impact of this MRD-adapted strategy on the progression-free and overall survival of patients.