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

Abstract

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.

Conflict of interest statement

Conflicts of Interest

The authors declare the following: RV: consultancy and research funding for Onyx Pharmaceuticals Inc. DSS: consultancy, honoraria, and board of directors or advisory committee membership for Millennium and Celgene. SJ: honoraria for Millennium, Celgene, Onyx Pharmaceuticals Inc., and Merck; board of directors or advisory committee membership for Ortho Biotech, Imedex, Medicom World Wide, Optum Health Education, and PER Group. AJJ: consultancy for Ortho Biotech, Celgene, Millennium, Onyx Pharmaceuticals Inc., Bristol-Myers Squibb, and Exelixis; honoraria for Ortho Biotech, Celgene, Millennium, Bristol-Myers Squibb, and Exelixis; speakers bureau for Ortho Biotech, Celgene, and Millennium; board of directors membership for Millennium, Onyx Pharmaceuticals Inc., and Bristol-Myers Squibb; advisory committee membership for Onyx Pharmaceuticals Inc. and Bristol-Myers Squibb. AKS: consultancy and research funding for Celgene, Millennium, Novartis, Bristol-Myers Squibb, and Onyx Pharmaceuticals Inc. KM: No relevant financial relationship(s) to disclose. NB: honoraria and speakers bureau for Celgene. AB: No relevant financial relationship(s) to disclose. LAK: consultancy for VLST Biotech, Threshold, and Onyx Pharmaceuticals Inc. SW: No relevant financial relationship(s) to disclose. AFW: employed by and equity ownership in Onyx Pharmaceuticals Inc. MW: research funding for Onyx Pharmaceuticals Inc.

© 2012 Blackwell Publishing Ltd.

Figures

Fig 1. PX-171-004 Study Design

ECOG=Eastern Cooperative Oncology Group

Fig 2. Time to Progression

Median time to progression = 4.6 months (95% CI 1.9–11.1).