Once-weekly carfilzomib combined with dexamethasone is feasible and effective for the treatment of patients with relapsed and/or refractory multiple myeloma, a study published in Blood has shown.1
Carfilzomib is a proteasome inhibitor that is approved by the U.S. Food and Drug Administration (FDA) for treatment of relapsed or refractory multiple myeloma in combination with dexamethasone or with lenalidomide plus dexamethasone, and as single-agent.
As a single-agent and with lenalidomide plus dexamethasone, carfilzomib is administered as a 10-minute intravenous infusion on days 1, 2, 8, 9, 15, and 16 of 28-day cycles (starting dose: 20 mg/m2 [cycle 1, days 1-2]; target dose: 27 mg/m2 thereafter). To reduce the number of administrations per cycle, researchers sought to evaluate the efficacy and safety of weekly carfilzomib with dexamethasone in the same treatment setting.
For the multicenter, single-arm, phase 1/2 CHAMPION-1 study, researchers enrolled 116 patients with multiple myeloma who had received 1 to 3 prior therapies. To determine the maximum tolerated dose in the phase 1 portion, all participants received carfilzomib at varying doses administered intravenously over 30 minutes on days 1, 8, and 15 of 28-day cycles.
In the phase 2 portion, patients received carfilzomib at the maximum tolerated dose of 70 mg/m2 given on the same schedule as the phase 1 portion plus dexamethasone 40 mg on days 1, 8, 15, and 22 (dexamethasone we omitted on day 22 starting with cycle 9).
Results showed that the overall response rate with the 70 mg/m2 dose, which was given to 104 patients in total, was 77%. Median progression-free survival was 12.6 months.
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In terms of safety, the most common grade 3 or worse adverse events experienced at the maximum tolerated dose were fatigue (11%) and hypertension (7%).
The findings ultimately suggest the further evaluation of this once-weekly regimen of carfilzomib and dexamethasone is warranted.
- Berenson JR, Cartmell A, Bessudo A, et al. CHAMPION-1: a phase 1/2 study of weekly carfilzomib and dexamethasone for relapsed or relapsed and refractory multiple myeloma [published online ahead of print May 12, 2016]. Blood. doi: 10.1182/blood-2015-11-683854.