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    Treatment of Newly Diagnosed Myeloma (excluding t-cell redirection therapy)

    (OA-70) Patient-Reported Outcomes (PROs) and Safety in Patients (Pts) With NDMM Achieving MRD Negativity and ≥CR (MRDneg) in the Phase 3 PERSEUS and CEPHEUS Trials

    Thursday, September 18, 2025
    15:32 - 15:40 East Coast USA Time
    Location: Hall FG
    Introduction: The Phase 3 PERSEUS and CEPHEUS trials showed daratumumab (Dara) plus bortezomib, lenalidomide, and dexamethasone (DVRd) improved MRDneg rate and PFS in both transplant-eligible (TE; PERSEUS) and -ineligible (TIE)/-deferred (TD; CEPHEUS) pts with NDMM. To understand the impact of achieving MRDneg on health-related quality of life (HRQoL), we assessed PROs and safety in pts from PERSEUS/CEPHEUS who achieved MRDneg vs those who remained MRDpos (or not in CR).

    Methods: Pts were randomized 1:1 to receive Dara + VRd induction/consolidation + DR maintenance vs VRd induction/consolidation + R maintenance (PERSEUS) or to receive DVRd vs VRd (CEPHEUS). MRDneg rate (10-5 and ≥CR) was a key secondary (PERSEUS) or primary (CEPHEUS) endpoint. PROs were evaluated at baseline and D1 Cycles [C] 1-8 and every 3rd C (CEPHEUS) or D1 C1-C3, pre-ASCT, C5, C7 and then Q12W (PERSEUS). PROs included concepts from the European Organisation for Research and Treatment of Cancer quality of life questionnaire core 30 (EORTC QLQ-C30). TEAE were graded with NCI-CTCAE v.5.

    Results:

    Median follow-up was 47.5 months (mo) in PERSEUS (median age 60 [range 31–70] y) and 58.7 mo in CEPHEUS (70 [31–80] y); 355/354 and 197/198 pts were assigned to DVRd/VRd, respectively. In PERSEUS, 267 (75.2%, D-VRd) and 168 (47.5%, VRd) pts, and in CEPHEUS 120 (60.9%, D-VRd) and 78 (39.4%, VRd) pts achieved MRDneg. Median treatment duration was longer in pts who achieved MRDneg vs MRDpos pts in PERSEUS (DVRd, 46.0 vs 41.3 mo; VRd, 45.9 vs 30.9 mo) and CEPHEUS (DVRd, 57.5 vs 22.5 mo; VRd, 56.6 vs 21.7 mo).

    The TEAE exposure-adjusted incidence rates (EAIR) per 100 pt-mo consistently favored pts who achieved MRDneg vs MRDpos pts in the DVRd arm across analyses in both PERSEUS (any TEAE, 156.82 vs 165.12; grade 3/4 TEAE, 11.89 vs 17.65; serious TEAE, 2.21 vs 3.21; TEAE leading to discontinuation, 0.19 vs 0.35; TEAE with outcome of death, 0.07 vs 0.19) and CEPHEUS (119.64 vs 235.78; 11.34 vs 13.15; 2.99 vs 3.99; 0.10 vs 0.38; 0.25 vs 0.76, respectively). EAIR for grade 3/4 infections/infestations and grade 3/4 neutropenia were lower in pts who achieved MRDneg vs MRDpos pts in PERSEUS (1.03 vs 1.67; 3.06 vs 4.39, respectively) and CEPHEUS (0.98 vs 1.92; 1.51 vs 2.15).

    PRO scores were similar for pts who achieved MRDneg vs MRDpos. With DVRd, mean change from BL (SE) in EORTC QLQ-C30 global health status in pts who achieved MRDneg vs MRDpos pts in PERSEUS (maintenance C34) was 7.6 (2.0) vs 3.3 (3.2), and in CEPHEUS (C36) was 8.5 (2.8) vs 4.2 (4.3). Similar safety and PRO trends were seen with VRd in both studies.

    Conclusions: In both TE and TIE/TD pts with NDMM, MRDneg achievement was associated with favorable PROs and exposure-adjusted safety outcomes vs MRDpos pts treated with DVRd or VRd. Pts achieving MRDneg stayed on treatment longer and maintained HRQoL despite this prolonged exposure. These data help reassure physicians that MRDneg pursuit in NDMM pts does not adversely impact safety or HRQoL.