Low-dose versus High-dose Carfilzomib with Dexamethasone (S1304) in Patients with Relapsed-Refractory Multiple Myeloma
Mené sur 121 patients atteints d’un myélome multiple réfractaire ou récidivant, cet essai de phase II compare l’efficacité, du point de vue de la survie sans progression, et la toxicité de faibles doses (27 mg/m2) et de hautes doses (56 mg/m2) de carfilzomib en combinaison avec la dexaméthasone
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.