Phase 2 dose-expansion study (PX-171-006) of carfilzomib, lenalidomide, and low-dose dexamethasone in relapsed or progressive multiple myeloma

Abstract

We previously reported a phase 1b dose-escalation study of carfilzomib, lenalidomide, and low-dose dexamethasone (CRd) in relapsed or progressive multiple myeloma where the maximum planned dose (MPD) was carfilzomib 20 mg/m2 days 1 and 2 of cycle 1 and 27 mg/m2 days 8, 9, 15, 16, and thereafter; lenalidomide 25 mg days 1 to 21; and dexamethasone 40 mg once weekly on 28-day cycles. Herein, we present results from the phase 2 dose expansion at the MPD, focusing on the 52 patients enrolled in the MPD cohort. Median follow-up was 24.4 months. In the MPD cohort, overall response rate (ORR) was 76.9% with median time to response of 0.95 month (range, 0.5-4.6) and duration of response (DOR) of 22.1 months. Median progression-free survival was 15.4 months. ORR was 69.2% in bortezomib-refractory patients and 69.6% in lenalidomide-refractory patients with median DOR of 22.1 and 10.8 months, respectively. A median of 9.5 (range, 1-45) carfilzomib cycles were started with 7.7% of patients requiring carfilzomib dose reductions and 19.2% discontinuing CRd due to adverse events (AEs). Grade 3/4 AEs included lymphopenia (48.1%), neutropenia (32.7%), thrombocytopenia (19.2%), and anemia (19.2%). CRd at the MPD was well tolerated with robust, rapid, and durable responses.

Trial registration: ClinicalTrials.gov NCT00603447.

Figure 1

Treatment schema. Cycles 13 to 18 (maintenance) carfilzomib dosing modified to days 1, 2, 15, 16. In cohort 6/7, 20 mg/m² was given on days 1 and 2 during cycle 1 and 27 mg/m² was given thereafter. D, day; IV, intravenous; MPD, maximum planned dose; PO, orally.

Figure 2

Progression-free survival. (A) PFS in the MPD cohort (n = 52). Twelve patients were censored for PFS because of alternate treatment (6 patients had achieved at least a partial response and decided to pursue other treatment). (B) PFS in the overall study population (N = 84). Nineteen patients were censored for PFS because of alternate treatment (7 patients had achieved at least a partial response and decided to pursue other treatment).