title: 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.
authors.affiliation: MD Anderson Cancer Center, Houston, TX;
authors.forename: Michael
authors.initials: M
authors.lastname: Wang
authors.forename: Tom
authors.initials: T
authors.lastname: Martin
authors.forename: William
authors.initials: W
authors.lastname: Bensinger
authors.forename: Melissa
authors.initials: M
authors.lastname: Alsina
authors.forename: David S
authors.initials: DS
authors.lastname: Siegel
authors.forename: Edward
authors.initials: E
authors.lastname: Kavalerchik
authors.forename: Mei
authors.initials: M
authors.lastname: Huang
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Orlowski
authors.forename: Ruben
authors.initials: R
authors.lastname: Niesvizky
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D003967:Diarrhea / Q000139:chemically induced; D018450:Disease Progression; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D000077269:Lenalidomide; D008231:Lymphopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D009364:Neoplasm Recurrence, Local; D009503:Neutropenia / Q000139:chemically induced; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects; D012074:Remission Induction; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D009842:Oligopeptides; D013792:Thalidomide; C524865:carfilzomib; D003907:Dexamethasone; D000077269:Lenalidomide