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 (CAR) T cells and bispecific T cell engagers have become integral components in the treatment of relapsed/refractory multiple myeloma. We report a 63-year-old male who received ciltacabtagene autoleucel CAR T cells and the GPRC5D × CD3 bispecific talquetamab for early relapse of his multiple myeloma. Nine months after CAR T therapy, he developed a symptomatic leukemic peripheral T cell lymphoma with cutaneous and intestinal involvement. Longitudinal single-cell RNA and T cell receptor sequencing of peripheral blood and bone marrow revealed two hyperexpanded CAR-carrying T cell clones. These expanded clones exhibited an exhausted effector-memory T cell transcriptional signature, and the neoplasm itself was sensitive to dexamethasone treatment. The immunophenotypic and transcriptional alterations of these abnormal T cells resembled those of T-large granular lymphocytic leukemia. Spatial transcriptomes of skin lesions confirmed the aberrant CAR-expressing T cells. Whole-genome sequencing revealed three distinct integration sites, within the introns of ZGPAT, KPNA4 and polycomb-associated noncoding RNAs. Before and after CAR T whole-genome analyses implicated clonal outgrowth of a TET2-mutated precursor propelled by additional subclone-specific loss of heterozygosity and other secondary mechanisms. This case highlights the evolution of a CAR-carrying peripheral T cell lymphoma following CAR T cell and bispecific T cell engager therapy, offering critical insights into the clonal evolution from a predisposed hematopoietic precursor to a mature neoplasm.