Carfilzomib is a next-generation, selective proteasome inhibitor being evaluated for the treatment of relapsed and refractory multiple myeloma. In this open-label, single-arm phase 2 study (PX-171-003-A1), patients received single-agent carfilzomib 20 mg/m2 intravenously twice weekly for 3 of 4 weeks in Cycle 1, then 27 mg/m2 for ≤12 cycles. Primary endpoint was overall response rate (ORR; ≥partial response). Secondary endpoints included clinical benefit response rate (≥minimal response), duration of response (DOR), progression-free survival, overall survival (OS), and safety. 266 patients were evaluable for safety, 257 for efficacy; 95% were refractory to their last therapy; 80% were refractory or intolerant to both bortezomib and lenalidomide. Patients had median of 5 prior lines of therapy, including bortezomib, lenalidomide, and thalidomide. ORR was 23.7% with median DOR of 7.8 months. Median OS was 15.6 months. Adverse events (AEs) were manageable without cumulative toxicities. Common AEs were fatigue (49%), anemia (46%), nausea (45%), and thrombocytopenia (39%). 33 patients (12.4%) experienced peripheral neuropathy, primarily Grades 1/2. Thirty-three patients (12.4%) withdrew due to an AE. Durable responses and an acceptable tolerability profile in this heavily-pretreated population demonstrate the potential of carfilzomib to offer meaningful clinical benefit. Registered at www.clinicaltrials.gov as #NCT00511238.
- Submitted May 2, 2012.
- Accepted July 16, 2012.
- Copyright © 2005 American Society of Hematology