The effect of carfilzomib (CFZ) in patients (Pts) with bortezomib (BTZ)-naive relapsed or refractory multiple myeloma (MM): Updated results from the PX-171-004 study.

Abstract

8026 Background: CFZ, a selective epoxyketone proteasome inhibitor, has potent, sustained action and lacks many BTZ-associated off-target activities. Durable activity has been observed in pts with advanced relapsed/refractory (R/R) MM, including those whose disease progressed on a BTZ-containing regimen. PX-171-004 is an ongoing phase (ph) II study of single-agent CFZ in pts with relapsed MM following 1–3 prior regimens. Here we present updated response, toxicity, and duration of response (DOR) data on BTZ-naive pts treated on this study. Methods: Pts in 2 sequential cohorts (Cohort 1 and Cohort 2) received IV CFZ on Days 1, 2, 8, 9, 15, 16 of every 28-day cycle (C), for up to 12 C. Both cohorts received 20 mg/m2 in C1; Cohort 2 dose escalated to 27 mg/m2 for C2–12. Primary endpoint was overall response rate (ORR) per IMWG criteria. Secondary endpoints were clinical benefit response (CBR), progression-free survival (PFS), DOR, overall survival (OS), time to progression (TTP), and safety. Results: 123 BTZ-naive pts were response-evaluable. Prior therapies included thalidomide (58%), lenalidomide (59%), alkylating agents (82%), and stem cell transplant (73%). 44 patients had disease refractory to the last prior therapy. Median TTP of 8.3 mo and median DOR of 13.1 mo were observed for Cohort 1; median TTP and DOR for Cohort 2 have not been reached. The most common grade (G) 3/4 AEs (all cause) were anemia (13%), lymphopenia (13%), pneumonia (13%), neutropenia (12%), and thrombocytopenia (11%). Treatment-emergent peripheral neuropathy (PN) was infrequent (18%) and mild. Only 1 case of G3 PN was observed. Overall, 49 pts (~40%) completed 12 C (~1 yr) and 27 pts continued CFZ therapy on an extension protocol. Conclusions: At the recommended phase III dose of CFZ, the 53% ORR is noteworthy for a single-agent regimen. Moreover, prolonged CFZ treatment is well-tolerated, with ~ 40% of pts completing 12 C and ~22% continuing treatment beyond 1 yr. Best response Cohort 1 N=59 20 mg/m2 n (%) Cohort 2 N=64 20/27 mg/m2 n (%) CR 2 (3) 1 (2) VGPR 8 (14) 17 (27) PR 15 (25) 16 (25) MR 10 (17) 6 (9) SD 13 (22) 12 (19) ORR (CR + VGPR + PR) 25 (42) 34 (53) CBR (ORR + MR) 35 (59) 40 (63)