Incidence of Immune Effector Cell-associated Neurotoxicity Among Patients Treated with CAR T-cell Therapy for Hematologic Malignancies: Systematic Review and Meta-analysis

Overview

Journal Front Neurol

Specialty Neurology

Date 2024 Oct 30

PMID 39474369

Authors

Min Woo Han

So Yeong Jeong

Chong Hyun Suh

Hyesun Park

Jeffrey P Guenette

Raymond Y Huang

Kyung Won Kim

Dok Hyun Yoon

Affiliations

Soon will be listed here.

Abstract

Objectives: We aim to assess the pooled incidence of immune effector cell-associated neurotoxicity syndrome (ICANS) in clinical trials and real-world studies of chimeric antigen receptor (CAR) T-cell therapy for hematologic malignancy and compare the incidences among different agents.

Methods: The PubMed, Embase, and Web of Science databases were searched for clinical trials and real-world studies. An inverse-variance weighting model was used to calculate pooled incidences and subgroup analyses. Multivariable analysis was conducted using binomial-normal modeling.

Results: Seventy-five trials comprising 3,184 patients were included. The overall pooled incidence was 26.9% (95% CI, 21.7-32.7%) for all-grade and 10.5% (95% CI, 8.1-13.6%) for high-grade ICANS. In subgroup analysis, cohorts with anti-CD19 drugs had significantly higher ICANS incidences than cohorts with other agents. The multivariable analysis demonstrated higher odds of ICANS in anti-CD19 drug studies for high-grade (OR, 4.6) compared to anti-BCMA drug studies. In 12 real-world studies, studies used axicabtagene ciloleucel with CD28 (54.0% all-grade, 26.4% high-grade) exhibited significantly higher rates of all-grade and high-grade ICANS than studies using tisagenlecleucel with 4-1BB (17.2% all-grade, 6.1% high-grade).

Conclusions: The overall incidences of ICANS with CAR T-cell therapy were 26.9% for all-grade and 10.5% for high-grade. Compared with other agents, patients with anti-CD19 drugs had a significantly increased risk of developing high-grade ICANS. Therefore, careful monitoring of ICANS should be considered for patients undergoing CAR T-cell therapy.

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