CAR T Therapy Induces Response in Majority of Patients With Relapsed Multiple Myeloma


Idecabtagene vicleucel induced progression-free survival up to 20 months and a complete response in one-third of patients with multiple myeloma who had relapsed multiple times and had received at least 3 previous lines of treatment.

A new chimeric antigen receptor (CAR) T-cell therapy induced a complete response in one-third of heavily pretreated patients with refractory and relapsed multiple myeloma. In addition, more than one-fourth of patients achieved a negative minimal residual disease (MRD) status.

The results of the phase 2 study of idecabtagene vicleucel (ide-cel) were published in The New England Journal of Medicine. The therapy is a B-cell maturation antigen–directed CAR T-cell therapy. The study treated 128 patients with ide-cel, who had disease after at least 3 previous regimens. They received ide-cel target doses of 150 x 106 to 450 x 106 CAR-positive T cells.

The primary end point of the study was overall response (partial response or better), and the key secondary end point was complete response or better. Additional secondary end points included time to response, duration of response, progression-free survival (PFS), overall survival, MRD, safety, pharmacokinetics, and immunogenicity.

"We have patients that are over 2 years out from their single infusion of CAR T cells and still in remission despite having no other treatment options when they were enrolled in this trial," Larry D. Anderson Jr, MD, PhD, co–first author and associate professor of internal medicine at UT Southwestern Medical Center, said in a statement. "The results mark a true breakthrough with unprecedented depth and duration of remissions from what we hope will be the first cellular therapy option to become available for myeloma patients.”

However, he added that it is too soon to know if any of the patients are cured, and many do relapse within 2 years. The therapy does buy patients more time until new treatment options are available, and during that time, they have a good quality of life with a low risk of severe adverse effects (AEs).

During the study, 4 patients were treated at a target dose of 150 x 106, 70 patients at 300 x 106, and 54 patients at 450 x 106. The median follow-up time was 13.3 months, and 94 patients (73%) had response, with 42 patients (33%) having a complete or stringent complete response. Approximately half (52%; n = 67) had a very good partial or better response.

Patients treated with the highest target dose had better responses and outcomes. At the lowest dose, 2 of 4 patients (50%) had a response compared with 48 of 70 patients (69%) at the medium dose, and 44 of 54 (81%) patients at the highest dose. One patient (25%) at the lowest dose had a complete response or better compared with 20 patients (29%) at the medium dose and 21 patients (39%) at the highest dose.

The majority (79%) of patients who had a complete or stringent response, or 26% of the full treated population, had MRD-negative status. “The fact that MRD-negative responses occurred in approximately a quarter of the patients highlights the depth of response induced by ide-cel,” the authors wrote.

The median duration of response was 10.7 months overall and slightly higher for the highest dose (11.3 months). The better the response, the longer it lasted: median response duration was 4.5 months in patients whose best response was a partial response (95% CI, 2.9-6.7), 10.4 months in patients with a very good partial response (95% CI, 5.1-11.3), and 19.0 months in patients with a complete or stringent complete response (95% CI, 11.3 to could not be estimated).

The findings on PFS were similar. While the overall median PFS was 8.8 months (95% CI, 5.6-11.6), it was 12.1 months (95% CI, 8.8-12.3) at the highest dose and 20.2 months (95% CI, 12.3 to could not be estimated) for patients who had a complete or stringent complete response.

All 128 patients experienced (AEs) and 127 patients experienced grade 3 or 4 events. Most AEs occurred within 8 weeks of the infusion. Eighty-four percent of patients also experienced cytokine release syndrome, which was mostly of grade 1 or 2, but 5 patients had grade 3 and 1 each had grade 4 or 5.

Forty-four patients (34%) died during the study, and 27 of these deaths were attributed to complications of multiple myeloma progression.

“One of the nice things we saw in this study was that the rates of severe CAR T-cell–related toxicities—called neurotoxicity and cytokine release syndrome—were very low in multiple myeloma compared to what we have seen with lymphoma CAR T-cell infusions," Anderson said. "The majority of people had some side effects, but most were low level and manageable, and I would say this therapy is often much better tolerated than a stem cell transplant, which most of these patients had already gone through."


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

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