MRD-Negative Response After VRd induction, HD-ASCT, and VRd consolidation in Transplant-Eligible Newly Diagnosed Multiple Myeloma: Phase 2 REMNANT Study with Broad Inclusion Criteria

High-dose melphalan with autologous stem-cell transplantation (HD-ASCT) prolongs progression-free survival (PFS) in transplant-eligible newly diagnosed multiple myeloma (TE-NDMM). However, most transplant trials exclude patients >65 years or those with poor performance status, aggressive disease, or significant comorbidities, limiting data on minimal residual disease (MRD)-negativity in these populations. REMNANT is a multicenter phase 2/3 study of TE-NDMM patients aged 18–75 years with broad eligibility criteria. This primary analysis reports MRD-negative complete response (CR) from the non-randomized phase 2 cohort. Patients received four cycles of bortezomib, lenalidomide, and dexamethasone (VRd) induction, HD-ASCT, and four cycles of VRd consolidation. MRD was tested in patients achieving ≥very good partial response (VGPR) post-consolidation. Between August 2020 and September 2024, 382 patients were enrolled (median age 63; 40% ≥65 years). MRD-negative CR was observed in 127 (33%) of 382 patients’ post-consolidation and 327 (86%) achieved ≥VGPR. The 12- and 24-month PFS were 88% and 79% (median follow-up 34.7 months), with comparable outcomes in patients <65 and ≥65 years. The most common adverse events of grade 3-4 were infections (44%) and cytopenias (21%). VRd induction, HD-ASCT, and VRd consolidation were effective and safe in a TE-NDMM cohort representative of the real-word NDMM population in Norway.