1. Daratumumab-based quadruplet therapy for transplant-eligible newly diagnosed multiple myeloma with high cytogenetic risk.
- Author
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Callander, Natalie, Silbermann, Rebecca, Kaufman, Jonathan, Godby, Kelly, Laubach, Jacob, Schmidt, Timothy, Sborov, Douglas, Medvedova, Eva, Reeves, Brandi, Dhakal, Binod, Rodriguez, Cesar, Chhabra, Saurabh, Bal, Susan, Anderson, Larry, Dholaria, Bhagirathbhai, Nathwani, Nitya, Hari, Parameswaran, Shah, Nina, Bumma, Naresh, Holstein, Sarah, Costello, Caitlin, Jakubowiak, Andrzej, Wildes, Tanya, Orlowski, Robert, Shain, Kenneth, Cowan, Andrew, Pei, Huiling, Cortoos, Annelore, Patel, Sharmila, Lin, Thomas, Giri, Smith, Costa, Luciano, Usmani, Saad, Richardson, Paul, Voorhees, Peter, and Chari, Ajai
- Subjects
Humans ,Multiple Myeloma ,Antibodies ,Monoclonal ,Female ,Male ,Middle Aged ,Aged ,Antineoplastic Combined Chemotherapy Protocols ,Chromosome Aberrations ,Adult ,Lenalidomide ,Dexamethasone - 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.
- Published
- 2024