Ciltacabtagene Autoleucel CAR−T-Cell Therapy for Patients With Multiple Myeloma

Results from the Phase 2 CARTITUDE-2 Trial

According to a phase 2, multicohort study recently published in Blood, ciltacabtagene autoleucel (cilta-cel) CAR-T-cell therapy produced favorable results among patients with relapsed/refractory multiple myeloma (MM) who had been previously exposed to noncellular anti-B-cell maturation antigen (BCMA) therapies. 

Dr Adam D. Cohen, MD, University of Pennsylvania, Philadelphia, Pennsylvania, and co-authors stated that although there are various treatments developed for MM that specifically target BCMA-expressing cells, “there have been reported cases of individuals who progressed after an initial anti-BCMA therapy, maintained BCMA expression, and responded to a different anti-BCMA therapy,” adding, “there is a need to identify the optimal sequencing of BCMA-directed agents in MM.” 

They aimed to reach the primary end point of minimal residual disease (MRD) negativity, and secondary end points of assessing incidence and severity of adverse events, overall response rate, rates of very good partial response (VGPR), complete remission (CR), stringent complete response, duration of response, and time to response. 

Patients ≥18 years of age with MM, evidence of progressive disease within 12 months of their last line of therapy or 6 months of prior therapy, and measurable disease at baseline were enrolled in this study. Eligible patients must have been treated with a proteasome inhibitor, immunomodulatory drug, anti-CD38 mAB, and noncellular BCMA-directed therapy prior to this trial. 

The 20 eligible patients in cohort C of this multicohort study were treated with ciltacabtagene autoleucel. Within this cohort, 35% of patients had bispecific antibodies as their most recent anti-BCMA treatment (n = 7), and 65% had antibody drug conjugates (n = 13). As of October 8, 2021, the data cutoff date, 13 patients (9 in the antibody drug conjugate arm and 4 in the bispecific antibody arm) remained enrolled in the study. 

At 11.3 months, the median follow-up, 7 of 20 patients achieved minimal residual disease (MRD) negativity. The overall response rate was 60% (95% confidence interval [CI], 36.1 to 80.9). The median duration of response was 11.5 months, and the median progression-free survival was 9.1 months. 

As for adverse events, grade 1 to 2 cytokine release syndrome (CRS) occurred in 12 (60%) patients; 4 patients had immune effector cell-associated neurotoxicity syndrome (2 had grade 3 to 4); none had parkinsonism. There were 7 deaths, 3 from progressive disease, and 4 from adverse events, with 1 treatment-related, and 3 unrelated to treatment. 

As primary and secondary end points were met, Dr Cohen et al concluded, “heavily pretreated patients with [R/R MM] who have been previously exposed to a noncellular BCMA-targeting agent can respond to cilta-cel, with 60% of patients achieving a response,” adding, “increased understanding of the best candidates for cilta-cel treatment after other BCMA-targeting therapy will be key to optimizing outcomes.” 

Source: 

Cohen AD, Mateos MV, Cohen YC, et al. Efficacy and safety of cilta-cel in patients with progressive multiple myeloma after exposure to other BCMA-targeting agents. Blood. 2023;141(3):219-230. doi:10.1182/blood.2022015526