Ide-Cel Shows Benefit vs Standard Regimens in Heavily Pretreated R/R Multiple Myeloma

Patients with triple-class–exposed relapsed and refractory multiple myeloma who were treated with idecabtagene vicleucel (ide-cel) showed significantly longer PFS and better therapy responses than patients on standard regimens, according to phase 3 trial findings published in The New England Journal of Medicine.

Ide-cel is a chimeric antigen receptor (CAR) T-cell therapy targeting the B-cell maturation antigen (BCMA) expressed mainly on myeloma cells, and it is approved for use in patients with relapsed or refractory multiple myeloma who have undergone at least 4 prior lines of therapy. The international, randomized, phase 3 KarMMa-3 trial (NCT03651128) was conducted to compare ide-cel with standard regimens in triple-class–exposed relapsed and refractory multiple myeloma following 2 to 4 previous lines of therapy.

Patients 18 years of age or older with measurable disease who had already received 2 to 4 lines of therapy and who had documented disease progression within 60 days of the last dose of the most recent therapy were enrolled in the study. Enrollment took place from May 2019 to April 2022, and all patients had Eastern Cooperative Oncology Group performance-status scores of 0 or 1. Previous lines of therapy included daratumumab, an immunomodulatory agent, and a proteasome inhibitor.

A total of 386 patients were enrolled, 66% of whom had triple-class–refractory disease, and 95% of whom had daratumumab-refractory disease.

Patients were randomized 2:1 to receive either ide-cel or standard-of-care therapy. A total of 254 patients received ide-cel, and 132 received standard regimens until disease progression, unacceptable toxic effects, or trial withdrawal. The standard regimens included daratumumab, pomalidomide, and dexamethasone (n = 43); daratumumab, bortezomib, and dexamethasone (n = 7); ixazomib, lenalidomide, and dexamethasone (n = 22); carfilzomib and dexamethasone (n = 30); or elotuzumab, pomalidomide, and dexamethasone (n = 30). The median follow-up was 18.6 months.

Median PFS was 13.3 months in the ide-cel cohort vs 4.4 months in the standard therapy group. The hazard ratio (HR) for disease progression or death in the standard-regimen group was 0.49 (95% CI, 0.38 to 0.65; P < .001).

In the ide-cel group, 71% of patients responded to therapy, compared with 42% of patients in the standard-regimen group (P < .001). Complete responses occurred in 39% of patients in the ide-cel group and 5% of patients in the standard-regimen cohort.

In terms of adverse events (AEs), 93% of patients who received ide-cel experienced grade 3 or higher AEs, compared with 75% of patients in the standard-regimen group. Cytokine release syndrome occurred in 88% of those who received CAR T-cell therapy, and 5% of those cases were grade 3 or higher. Neurotoxic events occurred in 15% of patients who received ide-cel, and 3% of those events were grade 3 or higher. OS data were not yet mature.

Overall, PFS and response rates were improved in the ide-cel cohort compared with the standard-regimen cohort in the study. However, the mechanisms behind ide-cel resistance have yet to be discerned.

“Given the prolonged progression-free survival and improved response that were observed with ide-cel therapy across multiple patient subgroups, ide-cel may provide benefit to patients with difficult-to-treat relapsed and refractory multiple myeloma,” the authors concluded. “These findings provide potential support for the use of ide-cel in patients with triple-class–exposed relapsed and refractory multiple myeloma, a population with poor survival outcomes.”

Reference

Rodriguez-Otero P, Ailawadhi S, Arnulf B, et al. Ide-cel or standard regimens in relapsed and refractory multiple myeloma. N Engl J Med. 2023;388(11):1002-1014. doi:10.1056/NEJMoa2213614