Carfilzomib 56 mg/m² twice-weekly in combination with dexamethasone and daratumumab (KdD) versus daratumumab in combination with bortezomib and dexamethasone (DVd): a matching-adjusted indirect treatment comparison

Abstract

Given the increasing use of frontline lenalidomide-based therapies in multiple myeloma (MM), there is an emerging need for lenalidomide-sparing regimens at relapse. Carfilzomib plus dexamethasone and daratumumab (KdD) and daratumumab plus bortezomib and dexamethasone (DVd) are lenalidomide-sparing triplet regimens that are approved for relapsed and/or refractory MM (R/RMM). In the absence of a head-to-head trial comparing these treatments, a matching-adjusted indirect treatment comparison (MAIC) was conducted to assess the efficacy and safety of KdD versus DVd. Results showed that treatment with KdD decreases the risk of progression or death versus DVd (HR 0.64; 95% confidence interval (CI): 0.46–0.90). Time-dependent analysis demonstrated a larger benefit for KdD after the first eight cycles. Unmatched subgroup analysis indicated that KdD may be particularly effective in lenalidomide-exposed and -refractory patients. The present analysis suggests that KdD improves outcomes compared with DVd in patients with R/RMM and may provide a rationale for a preferential treatment.

Keywords:

• Multiple myeloma
• lenalidomide-sparing triplet regimens
• matching-adjusted indirect treatment comparison

Acknowledgements

The authors sincerely thank Caroline Mattin (Amgen Ltd.) and Istvan Majer (Amgen (Europe) GmbH) for their work on this project.

Disclosure statement

K. Weisel has received honoraria from Abbvie, Adaptive, Amgen, BMS, Celgene, GSK, Janssen, Karyopharm, Roche, Sanofi, and Takeda; and has received research funding from Amgen, Celgene, Janssen, and Sanofi. A. Nooka has received honoraria from Adaptive, Amgen, BMS, GSK, Janssen, Karyopharm, Oncopeptides, Sanofi Pharmaceuticals, and Takeda; and has received research funding from Amgen, BMS, GSK, Janssen, Takeda, and Roche. E. Terpos has received honoraria from Amgen, BMS, Celgene, Genesis pharma SA, Janssen, and Takeda; and has received research funding from Genesis pharma SA and Takeda. A Spencer has received honoraria from AbbVie, Amgen, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialized Therapeutics Australia, Servier, and Takeda; and has received research funding from Amgen, Celgene, Haemalogix, Janssen, Servier, and Takeda. H Goldschmidt has received honoraria from Amgen, BMS, Celgene, Chugai, GSK, Janssen, Sanofi, and Novartis, and has received research funding from BMS, Celgene, Chugai, Incyte, Novartis, Molecular Partners, MSD, Mundipharma GmbH, Sanofi, and Takeda. F. Drinberger is an employee of Amgen GmbH and holds Amgen stocks. A Yusuf is an employee of Amgen Inc. and holds Amgen stocks. L. DeCosta is an employee of Amgen Ltd and holds Amgen Stocks. S. Kumar has received honoraria from Dr. Reddy's Laboratories, AbbVie, and Takeda; and has received research funding from AbbVie, Amgen, BMS, Carsgen, Celgene, Janssen, Kite, MedImmune, Merck, Novartis, Pharma, Roche, Sanofi, Takeda, and Tenebio.

Additional information

Funding

This analysis and the development of this manuscript were funded by Amgen (Europe) GmbH.