Journal Article

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

Silbermann, Rebecca, Pei, Huiling, Voorhees, Peter M., Giri, Smith, Lin, Thomas S., Cortoos, Annelore, Laubach, Jacob, Reeves, Brandi, Bal, Susan, Hari, Parameswaran, Holstein, Sarah A., Bumma, Naresh, Chari, Ajai, Patel, Sharmila, Shain, Kenneth H., Callander, Natalie S., Costa, Luciano J., Anderson, Larry D., Chhabra, Saurabh, Jakubowiak, Andrzej, Sborov, Douglas W., Medvedova, Eva, Rodriguez, Cesar, Orlowski, Robert Z., Shah, Nina, Richardson, Paul G., Dholaria, Bhagirathbhai R., Schmidt, Timothy M., Dhakal, Binod, Usmani, Saad Z., Godby, Kelly N., Costello, Caitlin, Cowan, Andrew J., Kaufman, Jonathan L., Nathwani, Nitya, Wildes, Tanya M.

2024

Overview

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 935yYg7rG1hc1uCFy66-b8

• Publisher: Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
• Subject: 692/699/1541/1990/804 / 692/699/67/1059/602 / Adult / Aged / Antibodies, Monoclonal - administration & dosage / Antibodies, Monoclonal - therapeutic use / Antineoplastic Combined Chemotherapy Protocols - adverse effects / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Biomedical and Life Sciences / Biomedicine / Cancer Research / Chromosome Aberrations / Dexamethasone - administration & dosage / Dexamethasone - therapeutic use / Female / Hematology / Humans / Immunotherapy / Inhibitor drugs / Lenalidomide - administration & dosage / Lenalidomide - adverse effects / Lenalidomide - therapeutic use / Male / Middle Aged / Monoclonal antibodies / Multiple myeloma / Multiple Myeloma - drug therapy / Multiple Myeloma - genetics / Multiple Myeloma - mortality / Multiple Myeloma - therapy / Oncology / Targeted cancer therapy