(CHICAGO, IL) – Single-agent carfilzomib is efficacious in patients with relapsed and double-refractory/intolerant multiple myeloma or disease that is refractory to all five approved classes of treatment, according to the updated results of a phase 2b trial presented at the 2012 American Association of Clinical Oncology Annual Meeting.

Previous studies have demonstrated that so-called “double-refractory/intolerant” patients—those with relapsed and refractory multiple myeloma who are refractory or intolerant to both bortezomib (BTZ) and immunomodulators (IMiDs; thalidomide or lenalidomide)—have few therapeutic options and a poor prognosis. David Samuel DiCapua Siegel, MD, PhD, Professor of Clinical Medicine, New York University Langone Medical Center, New York, said that carfilzomib, a next-generation proteasome inhibitor (PI), has shown durable single-agent activity in this patient population                                                                                                                          

The new open-label, single-arm phase 2b study examined carfilzomib clinical activity in patients with double-refractory/intolerant disease and in patients with disease refractory to all five approved classes of anti-myeloma treatments (ie, alkylators, anthracyclines, corticosteroids, IMiDs, and PIs). Patients received carfilzomib on Days 1, 2, 8, 9, 15, and 16 of 28-day cycles, (20mg/m2 in cycle 1; 27mg/m2 in  cycles 2–12), and were followed until a primary endpoint of overall response rate (ORR) was reached. Secondary endpoints included duration of response (DOR), overall survival, and safety.

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The study ORR was 22.9% with a median DOR of 7.8 months (N=266). In subgroup analyses, 228 patients (86%) with double-refractory/intolerant disease had ORRs of 20.6% and a median DOR of 7.4 months. Based on these data, Dr. Siegel and colleagues concluded that single-agent carfilzomib demonstrated clinically meaningful, durable responses in patients with double-refractory/intolerant multiple myeloma or disease refractory to all approved treatment classes.

“These results are notable for a next-generation PI and demonstrate the activity of single-agent carfilzomib in this patient group,” Dr. Siegel said. “Consistency of benefit across many clinically important subgroups, including those patients double refractory to bortezomib and lenalidomide, strengthens the conclusion that carfilzomib has significant activity in patients who have no remaining treatment options and thus have a critically important unmet need.”