Anti-BCMA CAR T cells(Allife Medicine)

Chimeric antigen receptor (CAR)-T cell therapies are being tested in many ongoing trials against hematologic malignancies and solid tumors. The incidence and profile of treatment-related adverse events are necessary when moving to clinical practice.

Published clinical trials on CAR-T cell therapies were collected from PubMed, Embase, Cochrane, and Web of Science databases between January 1, 2010, and August 27, 2024, with an updated search up to May 1, 2025, to extract tabular data on treatment-related adverse events. A logit-transformed random effects model was used to calculate the incidence and 95% CI of all-grade and grade 3 or higher treatment-related adverse events, with inter-study heterogeneity primarily assessed by I ² statistics. Differences between different antigen-binder, co-stimulation, cancer types, and specific subgroups were also explored in detail. The study was registered on PROSPERO (ID, CRD42024596383).

This systematic review and meta-analysis included 163 clinical trials involving 6342 patients. Of 4395 patients from 107 trials, 4312 (98.11% [95% CI, 97.65%-98.46%], I ² = 0.0%) had at least one adverse event of all-grade, and of 4248 patients from 103 trials, 3512 (82.67% [95% CI, 81.50%-83.78%], I ² = 82.8%) had at least one adverse event of grade 3 or higher. The most common all-grade adverse events and grade 3 or higher adverse events in hematological malignancies were cytokine release syndrome (81.50% [77.04%-85.43%]) and neutropenia (72.30% [62.94%-80.39%]), respectively. The most common all-grade adverse events and grade 3 or higher adverse events in solid tumors was lymphopenia (89.21% [45.31%-99.38%] and 51.96% [8.98%-92.87%]). Ciltacabtagene autoleucel was associated with a lower mean incidence of all-grade adverse events (Risk ratio [RR], 1.00; 95% CI, 0.99-1.01; Rank-score, 0.6341; I ² = 0.0%) and tisagenlecleucel were associated with lower grade 3 or higher adverse events (RR, 0.93; 95% CI, 0.86-1.02; Rank-score, 0.9738; I ² = 78.4%) compared with standard care and CAR T-cell therapies. Anti-CD19 CAR-T cells were associated with a lower mean incidence of grade 3 or higher adverse events compared with anti-BCMA CAR-T cells (RR, 0.93; 95% CI, 0.87-0.99; I ² = 78.4%). CAR-T cells containing 4-1BB costimulation had a lower incidence of grade 3 or higher adverse events than CAR-T cells containing CD28 costimulation (RR, 0.88; 95% CI, 0.81-0.95; I ² = 78.4%).

Our study provides comprehensive data on adverse events associated with different CAR-T cell treatments, maps a complete toxicity profile, and provides an important reference for clinicians to select and manage anti-cancer therapies.

This study was supported by the Changsha Natural Science Foundation of Hunan Provincial of China (Grant/Award Number: kq2208376 to HZ).

Chimeric antigen receptor T (CAR-T) cells targeting B cell maturation antigen (BCMA) have changed the treatment landscape for patients with relapsed and refractory multiple myeloma. However, T cell dysfunction associated with progressive disease and multiple prior lines of therapy (PLOT) raises concerns about the feasibility of consistently manufacturing effective CAR-T cells. We investigated the practicality of utilizing previously cryopreserved mobilized apheresis to generate potent anti-BCMA CAR-T cells. Paired patient samples collected longitudinally from (1) mobilized, unfractionated apheresis obtained before hematopoietic cell transplantation (mobHCT) and (2) apheresis obtained for commercial CAR-T manufacture (aphCAR) were directly compared head to head. The median time from transplant to commercial CAR-T infusion was 4.2 years (range, 2.5-12.5 years), and before CAR-T collection all patients were triple-class exposed. Analysis revealed that mobHCT samples exhibited a higher CD4:CD8 ratio and a greater proportion of naive T cells (CCR7⁺CD45RO^-) in both CD4 and CD8 compartments compared with aphCAR samples. CAR-T cells derived from mobHCT samples demonstrated superior expansion during manufacturing, enhanced interleukin-2 secretion, reduced expression of checkpoint inhibitors, improved cytotoxicity through multiple stimulation rounds, and enhanced mitochondrial function. These findings underscore the potential of utilizing cryopreserved mobilized apheresis collected earlier in the disease course to produce potent and metabolically robust CAR-T cells.