P169 | REAL-WORLD MINIMAL RESIDUAL DISEASE ANALYSIS IN TRANSPLANT-INELIGIBLE MULTIPLE MYELOMA PATIENTS TREATED WITH DARA-VMP VS. DARA-RD IN THE RANDOMIZED PHASE IV REAL MM TRIAL

Introduction. Daratumumab-bortezomib-melphalan-prednisone (D-VMP) and daratumumab-lenalidomide-dexamethasone (D-Rd) are standard-of-care regimens for newly diagnosed multiple myeloma (NDMM) patients (pts) ineligible for transplant (NTE). No prospective randomized trial compared D-VMP vs D-Rd, and data on the feasibility of minimal residual disease (MRD) assessment in real-life NTE settings are limited. Methods. REAL-MM is a randomized, multicenter, phase IV trial (NCT03829371), comparing D-VMP vs D-Rd in a real-life population of NTE NDMM pts. The study is actively enrolling. NTE NDMM pts (age ≥65 or with comorbidities) are being randomized 1:1 to D-VMP vs D-Rd and enrolled regardless of performance status and comorbidities. Stratification is based on IMWG frailty score and cytogenetic (CG) risk [high risk (HR)=del(17p) and/or t(14;16) and/or t(4;14)]. MRD is assessed by next-generation-flow in pts achieving ≥ very good partial response (VGPR) at +6, +12 months from randomization and yearly thereafter until +60 months. The primary endpoint of the trial is progression-free survival; the current preliminary analysis focuses on clinical response, MRD negativity (MRD-) rates and safety in the first year after randomization. Results At data cut-off (December 12, 2024), 163 pts were randomized (D-VMP n=81; D-Rd n=82). We excluded from the analysis 43 pts with < 1 year of follow-up, focusing on 120 pts (D-VMP n=61; D-Rd n=59) randomized before December 31, 2023. Baseline characteristics were balanced in D-VMP vs D-Rd arms: median age was 75 (IQR 72-78) vs 76 years (IQR 74-79); 34% vs 37% were frail; 25% vs 22% had HR CG. After a median follow-up of 14 months, ORR was 85% vs 78% (p=0.35) and ≥ VGPR rates were 67% and 59% (p=0.45). MRD- rates were 18% and 19% at 6 months (p=1.00), and 34% vs 27% at 12 months (p=0.43). Among HR CG pts, 12 months MRD- rates were 27% vs 38% (p=0.69) and among frail pts 29% vs 14% (p=0.28). No safety concerns emerged. The most frequent grade 3-4 adverse events were thrombocytopenia (13%) and neutropenia (8%) with D-VMP and neutropenia (28%) and infections (8%) with D-Rd. Conclusions. This preliminary descriptive analysis confirms the applicability of MRD assessment in a real-life NTE NDMM population, including 36% of frail patients. High MRD- rates were observed at 12 months in both arms, including HR CG and frail patients, supporting the use of daratumumab-based combinations in this setting. No new safety data emerged.