Daratumumab-Based Quadruplet Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma With High Cytogenetic Risk

Authors

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

Publication Date

4-22-2024

Journal

Blood Cancer Journal

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).Download video file.(327M, mp4)

Keywords

Humans, Multiple Myeloma, Antibodies, Monoclonal, Female, Male, Middle Aged, Aged, Antineoplastic Combined Chemotherapy Protocols, Chromosome Aberrations, Adult, Lenalidomide, Dexamethasone

DOI

10.1038/s41408-024-01030-w

PMID

38649340

PMCID

PMC11035596

PubMedCentral® Posted Date

April 2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes