MRD-Guided Therapy Could Change the Game in Newly Diagnosed Myeloma, Per MIDAS

The phase III MIDAS trial evaluated measurable residual disease (MRD)-guided consolidation strategies in transplantation-eligible patients with newly diagnosed multiple myeloma (MM). Aurore Perrot, MD, of Université de Toulouse, and colleagues found no significant advantage in achieving deeper MRD negativity for autologous stem-cell transplantation (ASCT)-based approaches versus extended quadruplet therapy in MRD-negative patients, nor for tandem ASCT over single ACST in MRD-positive patients. These results, which challenge traditional treatment paradigms, were recently published in the New England Journal of Medicine.

Patients who had completed induction therapy with isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) were enrolled and stratified by MRD status at 10^-5 sensitivity (assessed by next-generation sequencing, defined as <1 cancer cell per 100,000 normal cells) post-induction. The study team randomized participants who were MRD-negative to receive either ASCT followed by two cycles of Isa-KRd (ASCT group, n=485) or six cycles of Isa-KRd without transplantation (Isa-KRd group). The study team assigned MRD-positive patients to tandem ASCT (two transplants within a short interval) or single ASCT plus two Isa-KRd cycles (single ASCT group, n=233).

Among MRD-negative patients, 86% in the ASCT group and 84% in the Isa-KRd group achieved MRD negativity at 10-6 sensitivity prior to maintenance therapy (adjusted relative risk, 1.02; 95% CI, 0.95-1.10; P=0.64). This suggests extended Isa-KRd is comparable to ASCT in inducing responses, according to the published data. For MRD-positive patients, 32% in the tandem ASCT group versus 40% in the single ASCT group achieved this threshold (adjusted relative risk, 0.82; 95% CI, 0.58-1.15; P=0.31), with 15% of tandem ASCT patients failing to proceed to the second transplant, which may affect outcomes.

Disease progression occurred in five patients. Two non-progression-related deaths were reported during consolidation in the Isa-KRd and tandem ASCT arms.

These findings “suggest that the benefit of ASCT is questionable, at least in patients with an MRD-negative status after induction,” the authors concluded. Based on the results, Isa-KRd and other effective drug regimens show potential to match, or rival, transplantation in deepening responses for MRD-negative patients, while also offering a less invasive path to treatment. Additionally, single ASCT may suffice in cases of patients who are MRD-positive.

While these results are robust, the study’s median follow-up of 16.8 months for MRD-negative groups and 16.3 months for MRD-positive groups requires more mature data. “Our trial is ongoing, and longer follow-up is needed to assess progression-free survival and overall survival” with MRD-driven strategies, the authors stated.