MIDAS: Is ASCT needed in MM after reaching MRD-negativity with IsaKRD?

Patients with newly diagnosed multiple myeloma (MM) who were MRD-negative after isatuximab, carfilzomib, lenalidomide, and dexamethasone (IsaKRD) induction therapy did not benefit from autologous stem cell transplantation (ASCT) consolidation as compared to continued IsaKRD, results of the phase 3 MIDAS trial.

In the MIDAS trial (NCT04934475), 751 patients with previously untreated MM completed IsaKRD induction therapy (6 cycles) and had their MRD evaluated, as assessed by next-generation sequencing (10^-5). Hereafter, patients who were MRD-negative (10^-5; 63%) were randomised 1:1 to 6 additional cycles of IsaKRD (arm A) or to ASCT followed by 2 cycles of IsaKRD (arm B). Patients who were MRD-positive were randomised 1:1 to ASCT plus 2 cycles of IsaKRD (arm C) or to tandem ASCT (arm D). “We noticed that patients who were MRD-negative after induction therapy were less likely to have translocation (4; 14) (62% vs 81%; P=0.002) but more likely to have translocation (11; 14) (71% vs 40%; P<0.0001),” mentioned Dr Aurore Perrot (University of Toulouse, France). She presented the primary results of the study [1].

There was no difference between arm A and B, concerning the primary endpoint of post-consolidation MRD-negativity (10^-6) (84% vs 86%; P=0.64). Likewise, there was no significant difference between arms C and D concerning this endpoint (40% vs 32%; P=0.31; See Figure).

Figure: post-consolidation MRD negativity at 10^-6 in the intent-to-treat population [1]



MRD, minimal residual disease; p, p-value.

“Nausea, mouth ulceration, febrile neutropenia, sepsis, stomatitis, and mucosal inflammation were grade ≥3 adverse events that were more frequently observed in arm B than in arm A,” Dr Perrot discussed the safety of the two consolidation therapies. Next to that, vascular device infections were more common in arm D than in arm C.

In conclusion, ASCT consolidation, as compared to continued IsaKRD, did not improve post-consolidation MRD-negativity rates among patients with newly diagnosed MM who were MRD-negative after IsaKRD induction therapy. For MRD-positive patients, tandem ASCT did not offer additional MRD benefits over single ASCT. “MRD kinetics may vary by cytogenetics,” Dr Perrot pointed out. “Therefore, we should integrate genomic and MRD-based stratification for our ASCT selection process.”

1. Perrot A, et al. MRD-driven strategy following IsaKRD induction in transplant-eligible NDMM: primary endpoints of the phase 3 MIDAS trial. S205, EHA2025 Congress, 12–15 June, Milan, Italy.

 



Posted on 2 September 20252 September 2025