Investigational CAR T-Cell Therapy Leads to Response in Patients With Relapsed Multiple Myeloma

March 02, 2021

Treatment with an investigational B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell immunotherapy led to frequent and deep responses in patients with relapsed and refractory multiple myeloma, according to findings published recently in the New England Journal of Medicine.  

Patients in the trial received the investigational therapy – Idecabtagene vicleucel (ide-cel, bluebird bio and Bristol Myers Squibb) – after treatment with at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody. The primary endpoint was an overall response (partial response or better). 

The trial enrolled 140 patients, of whom 128 received ide-cel doses of 150×106 to 450×106 CAR-positive (CAR+) T cells. 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. Investigators confirmed minimal residual disease (MRD)–negative status (<10−5 nucleated cells) in 33 patients, representing 26% of all treated patients and 79% of the 42 patients who had a complete response or better. 

The median progression-free survival was 8.8 months, and overall survival was 19.4 months among treated patients. The median response duration and progression-free survival were numerically longer at the 450×106 dose. Almost all patients had grade 3 or 4 toxic effects.

Ide-cel showed durable persistence in blood, with 36% of patients who could be evaluated having detectable CAR+ T cells at 12 months. However, the investigators noted that the presence of these cells did not guard against disease recurrence, and it is unclear whether the patient became resistant to the CAR T cells or the T cells became functionally compromised. They concluded that the determination of long-term disease-free survival with ide-cel requires additional follow-up.