EXPRESS: Immune Effector Cell-Associated Neurotoxicity Syndrome in Hematological Malignancy Patients Treated with CAR-T Cell: A Systematic Review.

Authors

Kareem Latif, Jasmine Cha, Robert Niihara, Jerry Qi, Mohammad Dastjerdi, Mojtaba Akhtari

Published in

Journal of investigative medicine : the official publication of the American Federation for Clinical Research. Pages 10815589261497365. Oct 07, 2026. Epub Oct 07, 2026.

Abstract

Immune effector cell-associated neurotoxicity syndrome (ICANS) is a clinically significant complication of chimeric antigen receptor T-cell (CAR-T) therapy, with reported incidence varying across products and indications. However, the overall and product-specific risks of ICANS have not been comprehensively quantified. The aim of this study was to determine the pooled incidence of any-grade and severe (grade ≥3) ICANS across FDA-approved CAR-T products used in hematologic malignancies.
We performed a meta-analysis of prospective and retrospective studies evaluating six FDA-approved CAR-T products (axicabtagene ciloleucel, tisagenlecleucel, lisocabtagene maraleucel, brexucabtagene autoleucel, idecabtagene vicleucel, and ciltacabtagene autoleucel). The primary endpoint was incidence of any-grade ICANS; the secondary endpoint was incidence of grade ≥3 ICANS. Pooled incidence proportions were calculated using random-effects models. Heterogeneity was assessed using Cochran's Q and I² statistics.
Sixty analytic cohorts including 8,411 patients were analyzed. The pooled random-effects incidence of any-grade ICANS was 29.7% (95% CI, 24.3%-35.5%), and grade ≥3 ICANS occurred in 9.9% (95% CI, 7.4%-12.8%). Heterogeneity remained substantial for any-grade ICANS (Q=1822.40; I²=96.76%; τ²=0.22) and grade ≥3 ICANS (Q=965.44; I²=93.89%; τ²=0.11).Incidence varied markedly by product, with highest rates observed in CD28-based CD19 CAR-T therapies (axicabtagene ciloleucel and brexucabtagene autoleucel) and lower rates in 4-1BB-based CD19 and BCMA-targeted therapies.
Approximately one in four CAR-T recipients develop ICANS, with nearly one in ten experiencing severe neurotoxicity. Risk varies significantly by product, supporting the need for product-specific risk stratification, monitoring strategies, and toxicity mitigation approaches.

PMID:
42844744
Bibliographic data and abstract were imported from PubMed on 08 Oct 2026.

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