In a trial including heavily pretreated patients, idecabtagene vicleucel (ide-cel) demonstrated responses in most patients with relapsed/refractory multiple myeloma (RRMM), with most patients also showing grade 3 or 4 adverse events. Study results were published in The New England Journal of Medicine.
In the phase 2 KarMMA trial (NCT03361748), patients were assigned to receive ide-cel for RRMM at a target dosage ranging from 150×106 to 450×106 chimeric antigen receptor-positive (CAR+) T cells. Overall response, assessed by an independent review committee, was the primary study endpoint.
A total of 128 patients received the therapy, with most patients receiving either 300×106 or 450×106 CAR+ T cells. The median number of prior antimyeloma treatment regimens was 6 (range, 3 to 16).
The median follow-up was 13.3 months (range, 0.2 to 21.2), at which time 73% of patients achieved responses, with 33% showing a complete response or better. Minimal residual disease-negativity at a level of fewer than 10-5 nucleated cells was achieved in 79% of patients with a complete response or better.
Cytokine release syndrome occurred in 84% of patients and was reported at grade 3 or higher in 5% of all patients. Neurotoxicity was reported in 18% of patients, with 3% of all patients having grade 3 events. Overall, grade 3 or 4 adverse events were reported in 99% of patients, and most of these events were hematologic in nature; toxicities were considered consistent with prior reports. Approximately one-third (34%) of patients died during the study, with most fatalities deemed related to disease progression.
“Results of the KarMMa study support substantial antitumor activity for ide-cel across a target dose range of 150×106 to 450×106 CAR+ T cells,” the study investigators concluded in their report, noting a somewhat greater effectiveness with the highest dose. They considered observed toxicities in this study to be consistent with those of previous reports.
Munshi NC, Anderson Jr LD, Shah N, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med. 2021;384(8):705-716. doi:10.1056/NEJMoa2024850