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SYSTEMATIC REVIEW article

Front. Neurol.
Sec. Neuro-Oncology and Neurosurgical Oncology
Volume 15 - 2024 | doi: 10.3389/fneur.2024.1392831

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

Provisionally accepted
Min Woo Han Min Woo Han 1So Yeong Jeong So Yeong Jeong 2Chong Hyun Suh Chong Hyun Suh 3*Hyesun Park Hyesun Park 4Jeffrey P. Guenette Jeffrey P. Guenette 5Raymond Y. Huang Raymond Y. Huang 5Kyung Won Kim Kyung Won Kim 6Dok Hyun Yoon Dok Hyun Yoon 7
  • 1 College of Medicine, University of Ulsan, Ulsan, Republic of Korea
  • 2 Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi, Republic of Korea
  • 3 Asan Medical Center, College of Medicine, University of Ulsan, SONGPA-GU, Republic of Korea
  • 4 Dana-Farber Cancer Institution/Harvard Cancer Center, Boston, United States
  • 5 Department of Neuroradiology, Brigham and Women’s Hospital, Boston, United States
  • 6 Department of Radiology, Asan Medical Center, Seoul, Republic of Korea
  • 7 Department of Internal Medicine, Asan Medical Center, Seoul, Republic of Korea

The final, formatted version of the article will be published soon.

    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 binomialnormal modeling.Results Seventy-five trials comprising 3184 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% allgrade, 6.1% high-grade).The overall incidences of ICANS with CAR T-cell therapy were 26.9% for allgrade 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.

    Keywords: CAR T-cell, Immunotherapy, Immune Effector Cell-Associated Neurotoxicity Syndrome, Neurotoxicity, Hematologic malignances

    Received: 28 Feb 2024; Accepted: 23 Sep 2024.

    Copyright: © 2024 Han, Jeong, Suh, Park, Guenette, Huang, Kim and Yoon. 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: Chong Hyun Suh, Asan Medical Center, College of Medicine, University of Ulsan, SONGPA-GU, Republic of Korea

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