Carfilzomib ( Kyprolis ) is a selective proteasome inhibitor being evaluated for the treatment of relapsed and refractory multiple myeloma.
In an 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 or less.
The primary endpoint was overall response rate ( greater than or equal to partial response ). Secondary endpoints included clinical benefit response rate ( greater than or equal to 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 were manageable without cumulative toxicities. Common adverse reactions 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 adverse reactions.
Durable responses and an acceptable tolerability profile in this heavily pretreated population have demonstrated the potential of Carfilzomib to offer meaningful clinical benefit. ( Xagena )
Siegel DS et al, Blood 2012;120:2817-2825