Phase 2 dose-expansion study (PX-171-006) of carfilzomib, lenalidomide and low-dose dexamethasone in relapsed or progressive multiple myeloma
Mené sur 52 patients atteints d'un myélome multiple récidivant, cet essai de phase II évalue, du point de vue du taux de réponse globale, l'efficacité d'un traitement combinant carfilzomib, lénalidomide et dexaméthasone à faible dose (durée médiane de suivi : 24,4 mois)
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, 27 mg/m2 Days 8, 9, 15, 16 and thereafter; lenalidomide 25 mg Days 1-21, 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. This study is registered at clinicaltrials.gov, identifier: NCT00603447.