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Moreau, P.1; Stewart, A. K.2; Dimopoulos, M.-A.3; Siegel, D.4; Facon, T.5; Berenson, J.6; Raje, N.7; Berdeja, J. G.8; Orlowski, R. Z.9; Yang, H.10; Ma, H.10; Klippel, Z.10; Zahlten-Kumeli, A.10; Mezzi, K.10; Iskander, K.10; Mateos, M.-V.11

doi: 10.1097/01.HS9.0000560736.46354.bc
Poster Session I: Myeloma and other monoclonal gammopathies - Clinical

1University Hospital of Nantes, Nantes, France

2Mayo Clinic, Scottsdale, Arizona, United States

3National and Kapodistrian University of Athens, School of Medicine, Athens, Greece

4John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, United States

5Hôpital Claude Huriez, Lille University Hospital, Lille, France

6Institute for Myeloma & Bone Cancer Research, West Hollywood

7Massachusetts General Hospital Cancer Center, Boston

8Sarah Cannon Research Institute, Nashville

9The University of Texas MD Anderson Cancer Center, Houston

10Amgen Inc, Thousand Oaks, United States

11University Hospital Salamanca/IBSAL, Salamanca, Spain

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Carfilzomib (CFZ) combined with dexamethasone is approved to treat patients (pts) with relapsed and/or refractory multiple myeloma (RRMM), with CFZ given once-weekly at 70 mg/m2 (Kd70 QW) or twice-weekly at 56 mg/m2 (Kd56 BIW). No randomized trials have directly compared Kd70 QW with Kd56 BIW.

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We performed a post hoc comparison between pts who received Kd56 BIW in the ENDEAVOR trial and pts who received Kd70 QW in the A.R.R.O.W. or CHAMPION-1 trials.

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Data were analyzed from 3 trials of CFZ in RRMM: A.R.R.O.W. (240 pts in Kd70 QW arm; 2-3 prior therapies and refractory to most recent therapy), CHAMPION-1 (104 pts received Kd70 QW; 1-3 prior therapies), and ENDEAVOR (464 pts in Kd56 BIW arm; 1-3 prior therapies). Pts who received Kd70 QW in A.R.R.O.W. and CHAMPION-1 were pooled and compared with pts who received Kd56 BIW in ENDEAVOR. As study populations slightly varied among the 3 trials, an analysis of safety and efficacy was performed in a subgroup of pts who received 2-3 prior therapy lines and were not refractory to bortezomib (BTZ). Also, we performed regression analyses (controlling for age, ISS stage, BTZ and lenalidomide refractory status, and number of prior regimens) among all pts in the trials who received Kd70 QW or Kd56 BIW.

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Among BTZ non-refractory pts with 2-3 lines of prior therapy, median progression-free survival (PFS) was 12.1 months (95% CI 8.4-14.3) for Kd70 QW (n = 146) and 14.5 months (95% CI 10.2-NE) for Kd56 BIW (n = 217), and the overall response rate (ORR) was 69.9% (95% CI 61.7-77.2) for Kd70 QW and 72.4% (95% CI 65.9-78.2) for Kd56 BIW. The rate of grade ≥3 adverse events (Kd70 QW vs Kd56 BIW) was 67.6% and 85.3%; among adverse events of interest, the grade ≥3 rate was 1.4% and 5.1% for cardiac failure, 3.4% and 6.0% for renal failure, and 5.5% and 15.7% for hypertension. Kd70 QW represents a convenient and well-tolerated treatment modality for pts with RRMM. In a Cox proportional hazards model, the hazard ratio for PFS (Kd70 QW vs Kd56 BIW) was 0.91 (95% CI 0.69-1.19), and in a logistic regression model the odds ratio for ORR (Kd70 QW vs Kd56 BIW) was 1.12 (95% CI 0.74-1.69).

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This post hoc analysis suggests that once-weekly Kd70 has a comparable benefit-risk profile to twice-weekly Kd56.

© 2019 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2019 ASCO Annual Meeting. All rights reserved.

Copyright © 2019 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the European Hematology Association.