학술논문
Daratumumab-based quadruplet therapy for transplant-eligible newly diagnosed multiple myeloma with high cytogenetic risk
Document Type
article
Author
Natalie S. Callander; Rebecca Silbermann; Jonathan L. Kaufman; Kelly N. Godby; Jacob Laubach; Timothy M. Schmidt; Douglas W. Sborov; Eva Medvedova; Brandi Reeves; Binod Dhakal; Cesar Rodriguez; Saurabh Chhabra; Ajai Chari; Susan Bal; Larry D. Anderson; Bhagirathbhai R. Dholaria; Nitya Nathwani; Parameswaran Hari; Nina Shah; Naresh Bumma; Sarah A. Holstein; Caitlin Costello; Andrzej Jakubowiak; Tanya M. Wildes; Robert Z. Orlowski; Kenneth H. Shain; Andrew J. Cowan; Huiling Pei; Annelore Cortoos; Sharmila Patel; Thomas S. Lin; Smith Giri; Luciano J. Costa; Saad Z. Usmani; Paul G. Richardson; Peter M. Voorhees
Source
Blood Cancer Journal, Vol 14, Iss 1, Pp 1-8 (2024)
Subject
Language
English
ISSN
2044-5385
Abstract
Abstract In the MASTER study (NCT03224507), daratumumab+carfilzomib/lenalidomide/dexamethasone (D-KRd) demonstrated promising efficacy in transplant-eligible newly diagnosed multiple myeloma (NDMM). In GRIFFIN (NCT02874742), daratumumab+lenalidomide/bortezomib/dexamethasone (D-RVd) improved outcomes for transplant-eligible NDMM. Here, we present a post hoc analysis of patients with high-risk cytogenetic abnormalities (HRCAs; del[17p], t[4;14], t[14;16], t[14;20], or gain/amp[1q21]). Among 123 D-KRd patients, 43.1%, 37.4%, and 19.5% had 0, 1, or ≥2 HRCAs. Among 120 D-RVd patients, 55.8%, 28.3%, and 10.8% had 0, 1, or ≥2 HRCAs. Rates of complete response or better (best on study) for 0, 1, or ≥2 HRCAs were 90.6%, 89.1%, and 70.8% for D-KRd, and 90.9%, 78.8%, and 61.5% for D-RVd. At median follow-up (MASTER, 31.1 months; GRIFFIN, 49.6 months for randomized patients/59.5 months for safety run-in patients), MRD-negativity rates as assessed by next-generation sequencing (10–5) were 80.0%, 86.4%, and 83.3% for 0, 1, or ≥2 HRCAs for D-KRd, and 76.1%, 55.9%, and 61.5% for D-RVd. PFS was similar between studies and superior for 0 or 1 versus ≥2 HRCAs: 36-month PFS rates for D-KRd were 89.9%, 86.2%, and 52.4%, and 96.7%, 90.5%, and 53.5% for D-RVd. These data support the use of daratumumab-containing regimens for transplant-eligible NDMM with HCRAs; however, additional strategies are needed for ultra-high–risk disease (≥2 HRCAs). Video Abstract