Safety and Efficacy of Once-Weekly Carfilzomib (K) Dosing in Frail Patients (pts): A Subgroup Analysis from the Phase 3 A.R.R.O.W. Study

8027 Background: A.R.R.O.W. demonstrated superior progression-free survival (PFS) with once-weekly K (70 mg/m2)-dexamethasone (Kd70) vs twice-weekly K (27 mg/m2)-dexamethasone (Kd27) in relapsed and refractory multiple myeloma (RRMM) pts, regardless of age. Weekly Kd70 is US-approved for relapsed or refractory MM (1–3 prior therapy lines). For a comprehensive fitness measure, frailty scales were developed incorporating age, comorbidities, and functional status. (Palumbo Blood 2015; Facon Blood 2015). Here we assessed post hoc pt outcomes by frailty status. Methods: PFS and safety were assessed by treatment arm and a frailty algorithm incorporating age, medical history–derived Charlson Comorbidity Index, and ECOG performance status; pts with frailty scores of 0, 1, or ≥2 were classified as fit, intermediate (int), or frail, respectively. PFS was assessed with the Kaplan-Meier method. Safety was assessed in pts who received ≥1 treatment dose. Results: Pt distribution by frailty status was generally balanced between arms (Table). Once-weekly Kd70 vs twice-weekly Kd27 resulted in median PFS for fit, int, and frail pts of 15.7 vs 5.7 (mos; HR 0.53 [95% CI, 0.33–0.86]), 11.1 vs 7.7 mos (HR 0.81 [95% CI, 0.55–1.19]), and 10.3 vs 6.6 mos (HR 0.76 [95% CI, 0.49–1.16]), respectively. Rates of grade ≥3 treatment-emergent adverse events (TEAEs) of interest were similar between treatment arms across frailty subgroups (Table). In the once-weekly Kd70 subgroups, there was no grade ≥3 peripheral neuropathy (PN); grade ≥3 cardiac failure rates were ≤4%. Conclusions: Once-weekly Kd70 resulted in PFS benefits vs twice-weekly Kd27 with a favorable benefit/risk profile regardless of frailty score as defined. These results support weekly Kd70 as a treatment option for both fit and frail RRMM pts. Clinical trial information: NCT02412878. [Table: see text]