Neurotoxicity Associated with CD19-Targeted CAR-T Cell Therapies

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 incl...

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Bibliographic Details
Published in:CNS drugs Vol. 32; no. 12; pp. 1091 - 1101
Main Authors: Gust, Juliane, Taraseviciute, Agne, Turtle, Cameron J.
Format: Journal Article
Language:English
Published: Cham Springer International Publishing 01.12.2018
Springer Nature B.V
Subjects:
Animal models
Antigens
Antigens, CD19 - metabolism
Arthritis
Blood-brain barrier
Brain cancer
CD19 antigen
Cell activation
Cell therapy
Cerebrospinal fluid
Chimeric antigen receptors
Clinical trials
Corticosteroids
Cytokines
Cytokines - blood
Cytokines - cerebrospinal fluid
Edema
FDA approval
Headache
Humans
Immunologic Factors - therapeutic use
Immunotherapy
Immunotherapy, Adoptive - methods
Interleukin 6
Leading Article
Leukemia
Lymphocytes
Lymphocytes B
Lymphocytes T
Lymphoma
Medicine
Medicine & Public Health
Multiple myeloma
Neurology
Neurosciences
Neurotoxicity
Neurotoxicity Syndromes - epidemiology
Neurotoxicity Syndromes - immunology
Neurotoxicity Syndromes - metabolism
Neurotoxicity Syndromes - therapy
Pediatrics
Pharmacotherapy
Psychiatry
Psychopharmacology
Receptors, Antigen, T-Cell - metabolism
Seizures
Traumatic brain injury
Young adults
United States > US
ISSN:1172-7047, 1179-1934, 1179-1934
Online Access:Get full text
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Description
Summary: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.
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ISSN:1172-7047
1179-1934
1179-1934
DOI:10.1007/s40263-018-0582-9