Idecabtagene vicleucel, a B-cell maturation antigen (BCMA)–directed chimeric antigen receptor (CAR) T-cell therapy induced responses in a majority of heavily pretreated patients with refractory and relapsed multiple myeloma. Minimal residual disease (MRD)-negative status was achieved in 26% of treated patients. Almost all patients had grade 3 or 4 side effects, most commonly haematological side effects and cytokine release syndrome (CRS). The findings from the phase II KarMMa study are published on 25 February 2021 in The New England Journal of Medicine.

Dr. Nikhil Munshi of the Dana–Farber Cancer Institute, Harvard Medical School in Boston, MA, US and colleagues wrote in the study background that there is no standard of care for patients with multiple myeloma who have disease progression to immunomodulatory drugs, proteasome inhibitors, and anti-CD38 antibodies. The outcomes are poor, with infrequent complete responses, a median progression-free survival (PFS) of 3 to 4 months, and a median overall survival of 8 to 9 months.

Idecabtagene vicleucel showed promising efficacy in a phase I study in patients with relapsed or refractory multiple myeloma. These results prompted a pivotal KarMMa study to assess the efficacy and safety of idecabtagene vicleucel in patients with triple-class relapsed and refractory multiple myeloma and to evaluate pharmacokinetics, immunogenicity, and potential biomarkers for response and progression.

It was an open label, single-arm, multicentre, phase II study (NCT03361748). Patients received idecabtagene vicleucel target doses of 150×106 to 450×106 CAR-positive T-cells. The primary endpoint was an overall response defined as partial response or better. A key secondary endpoint was a complete response or better, comprising complete and stringent complete responses.

Of 140 patients enrolled, 128 received idecabtagene vicleucel. At a median follow-up of 13.3 months, 94 of 128 patients (73%) had a response, and 42 of 128 (33%) had a complete response or better.

MRD–negative status was confirmed in 33 patients, representing 26% of all 128 patients who were treated and 79% of the 42 patients who had a complete response or better.

The median PFS was 8.8 months (95% confidence interval, 5.6 to 11.6).

Common side effects among the 128 treated patients included neutropenia in 117 patients (91%), anaemia in 89 (70%), and thrombocytopenia in 81 (63%). CRS was reported in 107 patients (84%), including 7 (5%) who had events of grade 3 or higher. Neurotoxic effects developed in 23 patients (18%) and were of grade 3 in 4 patients (3%). No neurotoxic effects higher than grade 3 occurred.

Cellular kinetic analysis confirmed CAR-positive T-cells in 29 of 49 patients (59%) at 6 months and 4 of 11 patients (36%) at 12 months after infusion.

The authors concluded that the results of the KarMMa study support substantial antitumour activity for idecabtagene vicleucel across a target dose range of 150×106 to 450×106 CAR-positive T-cells. The 450×106 dose appeared to be somewhat more effective than the other doses. Grade 3 or higher CRS and neurotoxic effects were observed in no more than 6% of patients at all doses of CAR-positive T-cells. High-grade haematological side effects were common but transient. Overall, a small number of adverse events were fatal.

The study was funded by bluebird bio and Celgene, a Bristol-Myers Squibb company.


Munshi NC, Anderson Jr. LD, Shah, N, et al. Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma. N Engl J Med 2021;384:705-16. DOI: 10.1056/NEJMoa2024850.