Weekly carfilzomib, lenalidomide, and dexamethasone in relapsed or refractory multiple myeloma: A phase 1b study

Abstract

Twice-weekly carfilzomib (27 mg/m2 ) with lenalidomide-dexamethasone (KRd) is a standard-of-care in relapsed or refractory multiple myeloma (RRMM). This phase 1b study evaluated KRd with once-weekly carfilzomib in RRMM. Patients received carfilzomib (30-minute infusion; 56 or 70mg/m2 ) on days 1, 8, and 15; lenalidomide 25 mg on days 1-21; and dexamethasone 40 mg on days 1, 8, 15, and 22 (day 22 omitted for cycles 9+) of 28-day cycles. Primary objective was safety/tolerability; efficacy was a secondary objective. Fifty-six RRMM patients enrolled: 22 during dose evaluation (56-mg/m2 , n = 10; 70-mg/m2 , n = 12) and 34 during dose expansion (all initiated dosing at 70 mg/m2 ). After 2 fatal adverse events (AEs) during 70-mg/m2 dose expansion, dosage reduction to 56 mg/m2 was permitted. Results are presented for carfilzomib 56-mg/m2 (n = 10) and 70-mg/m2 groups (dose evaluation/expansion; n = 46). Median carfilzomib dose was 53.2 mg/m2 (56-mg/m2 group) and 62.4 mg/m2 (70-mg/m2 group). Grade ≥3 AE rates were 70.0% (56 mg/m2 ) and 69.6% (70 mg/m2 ). Overall response rates were 90.0% (56 mg/m2 ) and 89.1% (70 mg/m2 ); ≥very good partial response rates were 50.0% (56 mg/m2 ) and 73.9% (70 mg/m2 ). Once-weekly KRd was active with acceptable toxicity in RRMM, supporting further evaluation of this regimen.

Conflict of interest statement

Noa Biran: Honoraria and speakers' bureau participation for Celgene, Amgen, Takeda, and Sanofi; consulting or advisory role fees and reimbursement of travel, accommodations, or other expenses from Celgene, Amgen, and Takeda; and research funding from Celgene and Amgen.

David Siegel: Honoraria and consulting or advisory role fees for Celgene, Amgen, Merck, Janssen, BMS, Takeda, and Karyopharm; speakers' bureau participation for Celgene, Amgen, Merck, Janssen, BMS, and Takeda; and research funding from Celgene.

Jesus Berdeja: Research funding from Abbvie, Amgen, Bluebird, BMS, Celgene, Genentech, Glenmark, Janssen, Novartis, Poseida, Takeda, and Teva.

Noopur Raje: Consulting or advisory role fees for Amgen, Novartis, Takeda, Celgene, and Bluebird; and research funding from AstraZeneca and Eli Lilly.

R. Frank Cornell: Nothing to disclose.

Melissa Alsina: Honoraria from Janssen, Amgen, and Celgene; consulting or advisory role fees for Celgene and BMS; speakers' bureau participation for Janssen and Amgen; and research funding from BMS.

Tibor Kovacsovics: Research support from Abbvie and Amgen, and consulting fees from Amgen and Celgene.

Belle Fang: Employed by Amgen.

Amy Kimball: Employed by Amgen; stock or other ownership with Amgen, and stock ownership in WindMIL Therapeutics.

Ola Landgren: Research funding from National Institutes of Health, US Food and Drug Administration, Multiple Myeloma Research Foundation, International Myeloma Foundation, Leukemia and Lymphoma Society, Perelman Family Foundation, Rising Tides Foundation, Amgen, Celgene, Janssen, Takeda, Glenmark, Seattle Genetics, and Karyopharm; has served on honoraria/advisory boards for: Adaptive, Amgen, Binding Site, BMS, Celgene, Cellectis, Glenmark, Janssen, Juno, Pfizer; and serves on Independent Data Monitoring Committees for clinical trials led by Takeda, Merck, Janssen.

© 2019 The Authors. American Journal of Hematology published by Wiley Periodicals, Inc.

Figures

Figure 1

Swimmers plots for exposure to carfilzomib in the (A) 56‐mg/m2 group and (B) 70‐mg/m2 group