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CNS Drugs. 2018 Dec;32(12):1091-1101. doi: 10.1007/s40263-018-0582-9.

Neurotoxicity Associated with CD19-Targeted CAR-T Cell Therapies.

Author information

1
Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA.
2
Division of Pediatric Neurology, Department of Neurology, University of Washington, Seattle, WA, USA.
3
Department of Pediatrics, University of Southern California, Los Angeles, CA, USA.
4
Clinical Research Division and Integrated Immunotherapy Research Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. cturtle@fhcrc.org.
5
Department of Medicine, University of Washington, Seattle, WA, USA. cturtle@fhcrc.org.

Abstract

Neurotoxicity is an important and common complication of chimeric antigen receptor-T cell therapies. Acute neurologic signs and/or symptoms occur in a significant proportion of patients treated with CD19-directed chimeric antigen receptor-T cells for B-cell malignancies. Clinical manifestations include headache, confusion, delirium, language disturbance, seizures and rarely, acute cerebral edema. Neurotoxicity is associated with cytokine release syndrome, which occurs in the setting of in-vivo chimeric antigen receptor-T cell activation and proliferation. The mechanisms that lead to neurotoxicity remain unknown, but data from patients and animal models suggest there is compromise of the blood-brain barrier, associated with high levels of cytokines in the blood and cerebrospinal fluid, as well as endothelial activation. Corticosteroids, interleukin-6-targeted therapies, and supportive care are frequently used to manage patients with neurotoxicity, but high-quality evidence of their efficacy is lacking.

PMID:
30387077
DOI:
10.1007/s40263-018-0582-9

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