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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Vydáno v:	CNS drugs Ročník 32; číslo 12; s. 1091 - 1101
Hlavní autoři:	Gust, Juliane, Taraseviciute, Agne, Turtle, Cameron J.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Cham Springer International Publishing 01.12.2018 Springer Nature B.V
Témata:	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
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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.
AbstractList	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.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. 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.
Author	Taraseviciute, Agne Gust, Juliane Turtle, Cameron J.
AuthorAffiliation	5 Department of Medicine, University of Washington, Seattle, WA, USA 3 Department of Pediatrics, University of Southern California, Los Angeles, CA, USA 2 Division of Pediatric Neurology, Department of Neurology, University of Washington, Seattle, WA, USA 1 Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA, USA 4 Clinical Research Division and Integrated Immunotherapy Research Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
AuthorAffiliation_xml	– name: 3 Department of Pediatrics, University of Southern California, Los Angeles, CA, USA – name: 2 Division of Pediatric Neurology, Department of Neurology, University of Washington, Seattle, WA, USA – name: 1 Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA, USA – name: 4 Clinical Research Division and Integrated Immunotherapy Research Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA – name: 5 Department of Medicine, University of Washington, Seattle, WA, USA
Author_xml	– sequence: 1 givenname: Juliane surname: Gust fullname: Gust, Juliane organization: Center for Integrative Brain Research, Seattle Children’s Research Institute, Division of Pediatric Neurology, Department of Neurology, University of Washington – sequence: 2 givenname: Agne surname: Taraseviciute fullname: Taraseviciute, Agne organization: Department of Pediatrics, University of Southern California – sequence: 3 givenname: Cameron J. surname: Turtle fullname: Turtle, Cameron J. email: cturtle@fhcrc.org organization: Clinical Research Division and Integrated Immunotherapy Research Center, Fred Hutchinson Cancer Research Center, Department of Medicine, University of Washington
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/30387077$$D View this record in MEDLINE/PubMed
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Snippet	Neurotoxicity is an important and common complication of chimeric antigen receptor-T cell therapies. Acute neurologic signs and/or symptoms occur in a...
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SubjectTerms	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
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Title	Neurotoxicity Associated with CD19-Targeted CAR-T Cell Therapies
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