SYSTEMATIC REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicImmunological Advancements in Hematological Therapies: Exploring HSCT and CAR-T IntegrationView all 7 articles
Efficacy and safety of chimeric antigen receptor T-cell in the treatment of hematologic malignancy: an umbrella review of systematic review and meta-analysis
Provisionally accepted
- 1Department of Hematology, West China Hospital, Sichuan University, Chengdu, China, Chengdu, China
- 2State Key Laboratory of Wildlife Quarantine and Surveillance (Sichuan), Technology Center of Chengdu Customs,Chengdu, China, Chengdu, China
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Background: This umbrella review consolidates data from systematic reviews and meta-analyses on the efficacy and safety of Chimeric Antigen Receptor T-cell (CART) therapy in hematologic malignancies. The aim is to assess CAR-T efficacy across different malignancies, identify key safety concerns, and provide clinical recommendations. Methods: 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. Results: A total of 105 meta-analyses met the inclusion criteria. CD19-targeted CART 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. Conclusions: 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.
Keywords: CAR-T therapy, Acute Lymphoblastic Leukemia, Diffuse large B-celllymphoma, meta-analyses, Umbrella review
Received: 09 Apr 2025; Accepted: 31 Oct 2025.
Copyright: © 2025 Yu, Jing, Xie, Min, Li, Wang and Niu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ting Niu, niuting@wchscu.cn
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