Isa-KRd Consolidation Rivals Up-Front Transplant for 10-6 MRD Clearance in Newly Diagnosed Myeloma

Measurable-residual-disease–guided phase 3 MIDAS trial (NCT04934475) randomized 718 transplant-eligible NDMM patients after Isa-KRd induction by post-induction MRD10-5 status. In MRD-negative (n = 485) disease, deep MRD10-6 negativity before maintenance was identical whether patients went to ASCT + 2 cycles Isa-KRd or skipped transplant for 6 more Isa-KRd cycles (86% vs 84%; RR 1.02, P = 0.64). In MRD-positive (n = 233) disease, tandem ASCT failed to beat single ASCT + Isa-KRd (32% vs 40% MRD10-6; RR 0.82, P = 0.31), with 15% unable to complete the second graft. Median follow-up 17 mo showed no new safety signals and only seven early progressions/deaths across arms. Historical FORTE data place MRD10-6 negativity/ 4-year PFS after KRd + ASCT at ~71% in patients with zero high-risk cytogenetic abnormalities (HRCAs), 60% with 1 HRCA and 39% with two or more HRCAs, underscoring the potency of Isa-KRd without transplant, more so in patients without HRCAs.