Low-dose versus High-dose Carfilzomib with Dexamethasone (S1304) in Patients with Relapsed-Refractory Multiple Myeloma

Abstract

Purpose: Treatment of multiple myeloma (MM) has evolved tremendously and optimal utilization of available therapies will ensure maximal patient benefits. Experimental Design: We report the SWOG randomized phase 2 trial (S1304) comparing twice-weekly low-dose (27 mg/m²; Arm 1) to high-dose carfilzomib (56 mg/m²; Arm 2), both with dexamethasone, administered for 12 cycles (11 months) for relapsed and/or refractory MM with up to six prior lines of therapy (NCT01903811). The primary endpoint was progression-free survival (PFS), and patients on Arm 1 could crossover to Arm 2 after progression on treatment. Results: Among 143 enrolled patients, of whom 121 were eligible and analyzable, the overall response rate was 42.8%, with no significant difference between the arms (p=0.113). Also, neither the median PFS (5 months and 8 months, respectively; HR: 1.061, 80% Wald CI 0.821, 1.370; p=0.384) nor the median overall survival were significantly different (26 and 22 months, respectively; HR: 1.149, 80% Wald CI 0.841, 1.571; p=0.284). Sixteen patients crossed over to Arm 2 with a median PFS benefit of 3 months. Certain adverse events (AE) were more frequent in Arm 2, including fatigue, thrombocytopenia and peripheral neuropathy, but there was no significant difference in cardiopulmonary AEs. Conclusions: This randomized trial did not support a benefit of fixed-duration, twice-weekly 56 mg/m² dosing of carfilzomib over the 27 mg/m² dose for the treatment of relapsed and/or refractory MM. However, treatment to progression in earlier patient populations with high-dose carfilzomib using different schedules should still be considered as part of the standard of care.