What is the efficacy of chimeric antigen receptor (CAR) T-cell therapy for multiple myeloma?

Updated: Dec 17, 2020
  • Author: Sameh Gaballa, MD, MS; Chief Editor: Emmanuel C Besa, MD  more...
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Several myeloma target antigens are being investigated in clinical trials of patients with R/R multiple myeloma, including B-cell maturation antigen (BCMA), CD38, CD138, SLAMF7, and natural killer group 2D. Idecabtagene vicleucel (ide-cel; bb2121) is a BCMA-targeted CAR T cell that showed excellent activity in a phase I study; 33 patients with high risk R/R myeloma were enrolled, and 85% had a response (45% CR). All 16 patients who had a response and who could be evaluated for MRD had MRD-negative status. [26]  

These excellent results were confirmed in a larger phase II study (KarMMa); the initial results showed an ORR of 73% with a median PFS of 8.6 months in heavily pre-treated patients with R/R multiple myeloma. Moreover, the rates of severe grade 3 or higher toxicity were relatively low (cytokine release syndrome, 5%; neurotoxicity: 3%). [27]  Based on this study, Ide-cel was granted breakthrough therapy designation by the FDA and a Biologics License Application (BLA) is currently under review.

Another promising CAR T agent, developed in China, is LCAR-B38, which targets 2 distinct BCMA epitopes with theoretical high avidity and distinguishes LCAR-B38M from other BCMA-targeting CAR T constructs. The phase I (LEGEND-2) study enrolled 57 patients with R/R multiple myeloma and 88% of patients achieved a response (74% CR). Moreover, the toxicity profile was favorable, with a grade 3 cytokine release syndrome rate of 7% and only one patient experiencing grade 1 neurotoxicity. After a median follow-up of 19 months, the median OS was not reached. [28]  

The same construct is currently undergoing a phase I/II study in the United States and Japan (CARTITUDE-1) under the name JNJ-4528. In the phase Ib part of the study in 29 patients, all patients achieved a response; 22 (76%) achieved a stringent CR. Neurotoxicity was reported in 4 patients (grade I-2 in three patients, grade 3 in one patients). However, there was one death from cytokine release syndrome, so further results from the phase II part of the study are needed to clarify the safety profile of the construct. [29]

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