Daratumumab-based quadruplet therapy for transplant-eligible newly diagnosed multiple myeloma with high cytogenetic risk

oleh: 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

Format: Article
Diterbitkan: Nature Publishing Group 2024-04-01

Deskripsi

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