Daratumumab Plus Bortezomib, Melphalan, and Prednisone Versus Bortezomib, Melphalan, and Prednisone in Transplant-Ineligible Newly Diagnosed Multiple Myeloma: Frailty Subgroup Analysis of ALCYONE.

Abstract Background : In the phase 3 ALCYONE study, daratumumab plus bortezomib/melphalan/prednisone (D-VMP) versus bortezomib/melphalan/prednisone (VMP) significantly improved progression-free survival (PFS) and overall survival (OS) in transplant-ineligible, newly diagnosed multiple myeloma (NDMM) patients. We present a subgroup analysis of ALCYONE by patient frailty status. Patients and Methods : Frailty assessment was performed retrospectively using age, Charlson Comorbidity Index, and baseline Eastern Cooperative Oncology Group performance status score. Patients were classified as fit (0), intermediate (1), or frail (≥2); a non-frail category combined fit and intermediate patients. Results : Among randomized patients (D-VMP, n=350; VMP, n=356), 391 (55.4%) were non-frail (D-VMP, 187 [53.4%]; VMP, 204 [57.3%]) and 315 (44.6%) were frail (163 [46.6%]; 152 [42.7%]). After 40.1-months median follow-up, non-frail patients had longer progression-free survival (PFS) and overall survival (OS) than frail patients, but benefits of D-VMP versus VMP were maintained across subgroups: PFS non-frail (median, 45.7 vs 19.1 months; HR, 0.36; P Conclusion : Our findings support the clinical benefit of D-VMP in transplant-ineligible NDMM patients enrolled in ALCYONE, regardless of frailty status. MicroAbstract In the global phase 3 ALCYONE study, daratumumab plus bortezomib/melphalan/prednisone (D-VMP) significantly improved outcomes versus VMP in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). In this subgroup analysis of ALCYONE, frailty was assessed retrospectively among all randomized patients (D-VMP, n=350; VMP, n=356). Improved efficacy with D-VMP versus VMP was observed across frailty subgroups, with no new safety concerns.