An open-label, single-arm, phase 2 study of single-agent carfilzomib in patients with relapsed and/or refractory multiple myeloma who have been previously treated with bortezomib.

Carfilzomib is a next-generation proteasome inhibitor that selectively and irreversibly binds to its target. In clinical studies, carfilzomib has shown efficacy in patients with relapsed and/or refractory multiple myeloma (MM) and has demonstrated a tolerable safety profile. In this phase 2, open-label, multicentre clinical trial, 35 patients with relapsed and/or refractory MM following 1-3 prior therapies, including at least one bortezomib-based regimen, received carfilzomib 20 mg/m(2) in a twice-weekly, consecutive-day dosing schedule for ≤12 monthly cycles. The best overall response rate (ORR) was 17·1% and the clinical benefit response rate (ORR + minimal response) was 31·4%. The median duration of response was >10·6 months and the median time to progression was 4·6 months. The most common adverse events were fatigue (62·9%), nausea (60·0%), and vomiting (42·9%). No exacerbation of baseline peripheral neuropathy was observed. Single-agent carfilzomib was generally well tolerated for up to 12 treatment cycles and showed activity in patients with relapsed and/or refractory MM who had received prior treatment with bortezomib. These data, combined with an acceptable toxicity profile, support the potential use of carfilzomib in patients with relapsed and/or refractory MM and warrant continued investigation of carfilzomib as single agent or in combination with other agents.