Efficacy and safety of chimeric antigen receptor T-cell in the treatment of hematologic malignancy: an umbrella review of systematic review and meta-analysis.

Abstract

<h4>Background</h4>This umbrella review consolidates data from systematic reviews and meta-analyses on the efficacy and safety of Chimeric Antigen Receptor T-cell (CAR-T) therapy in hematologic malignancies. The aim is to assess CAR-T efficacy across different malignancies, identify key safety concerns, and provide clinical recommendations.<h4>Methods</h4>We conducted a thorough search of PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews up to May 2024. Systematic reviews and meta-analyses evaluating CAR-T efficacy in hematologic malignancies were included. The AMSTAR tool was used to assess methodological quality, and the GRADE system was employed to evaluate the quality of evidence for each outcome.<h4>Results</h4>A total of 105 meta-analyses met the inclusion criteria. CD19-targeted CAR-T therapies demonstrated superior efficacy in acute lymphoblastic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL), particularly in relapsed or refractory cases (high-quality). However, CAR-T monotherapy showed reduced efficacy in central nervous system lymphoma (CNSL) (middle-quality). Combination therapies, particularly CAR-T with HSCT, improved complete response rates but were associated with increased severe adverse events, such as CRS and neurotoxicity (high-quality). Axi-cel was found to carry a higher risk of ICANS and neutropenia compared to Tisa-ce (high-quality), likely due to its CD28 costimulatory domains, which enhance T-cell activation.<h4>Conclusions</h4>CAR-T therapy demonstrates promising clinical outcomes in ALL and DLBCL, but significant safety concerns remain. Combining CAR-T with therapies such as HSCT improves efficacy but also heightens the risk of severe toxicities. Future research should focus on optimizing CAR-T constructs, refining preconditioning regimens, and identifying predictive biomarkers to personalize treatment and mitigate risks in vulnerable populations.<h4>Systematic review registration</h4>https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024581782.