Final results of PX-171-003-A0, part 1 of an open-label, single-arm, phase II study of carfilzomib in patients with relapsed and refractory multiple myeloma

Final results of PX-171-003-A0, part 1 of an open-label, single-arm, phase II study of carfilzomib in patients with relapsed and refractory multiple myeloma

S. Jagannath, R. Vij, K. Stewart, et al

Methods: The multicenter, open-label PX-171-003-A0 study enrolled 46 multiple myeloma patients who had relapsed after > 2 therapies, had failed bortezomib (Velcade) and at least one immunomodulatory agent (thalidomide or lenalidomide [Revlimid]). They had also been refractory to their last treatment, defined as progressing ≤ 60 days of their last therapy or having < 25% response to it. Patients received carfilzomib (20 mg/m2 IV d 1, 2, 8, 9, 15, and 16 every 28 days) for up to 12 cycles. Clinical benefit response (CBR) was defined as molecular response (MR) or better.

Results: Thirty-six (78%) had progressed ≤ 60 days of last therapy and 10 (22%) had no response to last therapy. Thirty-nine patients completed at least 1 cycle of carfilzomib, had measurable M-protein, and were evaluable for response. The median number of prior therapies was 5 (range 2–15). All patients had previously received bortezomib, 91% prior thalidomide, and 89% prior lenalidomide. Also, 83% had prior stem cell transplantation and all had failed combinations including anthracyclines (80%) and/or alkylating agents (94%). Patients received a median of 3 cycles (range 1–12), and 13 patients completed ≥ 6 cycles.

The CBR was 26% (10/39 evaluable patients), including 5 partial responses and 5 MRs. Five bortezomib-refractory patients (19%) achieved MR (3) or PR (2). Median progression-free survival was 5.1 months.

The most common adverse events were fatigue, anemia, thrombocytopenia, nausea, upper respiratory infection, increased creatinine, and diarrhea. Peripheral neuropathy occurred in < 10% of patients.

Conclusions: Single-agent carfilzomib is active (18% PR; 8% MR) in heavily pretreated refractory MM patients who have failed all proven agents. Median response duration was 7.4 months. The drug is well tolerated, producing low rates of peripheral neuropathy.