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A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma
David S Siegel1, Thomas Martin, Michael Wang
1John Theurer Cancer Center at Hackensack University, Hackensack, NJ 07601, USA. dsiegel@hackensackumc.org
Abstract:
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/m(2) intravenously twice weekly for 3 of 4 weeks in cycle 1, then 27 mg/m(2) for ≤ 12 cycles. The primary endpoint was overall response rate (≥ partial response). Secondary endpoints included clinical benefit response rate (≥ minimal response), duration of response, progression-free survival, overall survival, and safety. A total of 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. Overall response rate was 23.7% with median duration of response of 7.8 months. Median overall survival was 15.6 months. Adverse events (AEs) were manageable without cumulative toxicities. Common AEs were fatigue (49%), anemia (46%), nausea (45%), and thrombocytopenia (39%). Thirty-three patients (12.4%) experienced peripheral neuropathy, primarily grades 1 or 2. Thirty-three patients (12.4%) withdrew because of an AE. Durable responses and an acceptable tolerability profile in this heavily pretreated population demonstrate the potential of carfilzomib to offer meaningful clinical benefit. This trial was registered at www.clinicaltrials.gov as #NCT00511238.
Insights
Carfilzomib demonstrated a 23.7% overall response rate in patients with relapsed/refractory multiple myeloma. This proteasome inhibitor showed durable responses and manageable side effects in heavily pretreated individuals.
Area of Science:
- Oncology
- Hematology
- Pharmacology
Background:
- Multiple myeloma is a hematologic malignancy characterized by uncontrolled plasma cell proliferation.
- Relapsed and refractory multiple myeloma present significant treatment challenges, necessitating novel therapeutic agents.
- Carfilzomib, a next-generation proteasome inhibitor, targets underlying mechanisms of multiple myeloma.
Purpose of the Study:
- To evaluate the efficacy and safety of single-agent carfilzomib in patients with relapsed and refractory multiple myeloma.
- To determine the overall response rate (ORR) as the primary endpoint.
- To assess secondary endpoints including duration of response, progression-free survival, overall survival, and safety profile.
Main Methods:
- An open-label, single-arm, phase 2 study (PX-171-003-A1) was conducted.
- Patients received carfilzomib 20 mg/m² intravenously twice weekly for cycle 1, escalated to 27 mg/m² for up to 12 cycles.
- 257 patients were evaluable for efficacy, with 95% refractory to last therapy and 80% refractory/intolerant to bortezomib and lenalidomide.
Main Results:
- The overall response rate (ORR) was 23.7%, with a median duration of response of 7.8 months.
- Median overall survival was 15.6 months.
- Common adverse events included fatigue (49%), anemia (46%), and nausea (45%); peripheral neuropathy occurred in 12.4%.
Conclusions:
- Carfilzomib demonstrated durable responses and an acceptable tolerability profile in a heavily pretreated multiple myeloma population.
- The drug offers meaningful clinical benefit for patients with relapsed and refractory disease.
- Carfilzomib represents a valuable therapeutic option for advanced multiple myeloma.
