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Cited by 216CAR-T cell therapy researchAutoimmune and Inflammatory Disorders ResearchCancer Immunotherapy and Biomarkers

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Cytokine release syndrome and neurotoxicity following CAR T-cell therapy for hematologic malignancies

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Freyer, Craig W., Porter, David L.·2020·Journal of Allergy and Clinical Immunology
DOI 10.1016/j.jaci.2020.07.025
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Abstract

Chimeric antigen receptor T cells are a new and exciting immunotherapeutic approach to managing cancer, with impressive efficacy but potentially life-threatening inflammatory toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Patients with severe CRS may develop capillary leak syndrome and disseminated intravascular coagulation, with a cytokine signature similar to that of macrophage activation syndrome/hemophagocytic lymphohistiocytosis. Moderate-to-severe CRS is managed with the IL-6 receptor antagonist tocilizumab with or without corticosteroids, with questions remaining regarding the optimal management of nonresponders. ICANS is an inflammatory neurotoxicity typically occurring after CRS and characterized by impaired blood-brain barrier integrity. Symptoms of encephalopathy range from mild confusion and aphasia to somnolence, obtundation, and in some cases seizures and cerebral edema. ICANS is currently managed with corticosteroids; however, the optimal dose and duration remain to be determined. Little information is available to guide the management of patients with steroid-refractory ICANS. Numerous cytokine-targeted therapies have been proposed to manage these inflammatory toxicities, but few clinical data are available. Management of inflammatory toxicities of chimeric antigen receptor T cells often requires multidisciplinary management and intensive care, during which allergists and immunologists may…

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Metadata

Authors
Freyer, C. W., & Porter, D. L.
Affiliations
Hospital of the University of Pennsylvania (US)
ORCID
Venue
Journal of Allergy and Clinical Immunology
Publisher
Elsevier BV
Published
2020-11
Volume
146
Issue
5
Pages
940-948
ISSN
0091-6749 (ISSN-L)
DOI
10.1016/j.jaci.2020.07.025
OpenAlex
W3047493249
Cited by
216
References
0
Citations by year
2026: 40 · 2025: 63 · 2024: 39 · 2023: 37 · 2022: 23 · 2021: 13 · 2020: 1
FWCI
1.99
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Allergy and Clinical Immunology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Oncology › CAR-T cell therapy research
  • Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords
cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, CAR T-cell therapy, hematologic malignancies, capillary leak syndrome, disseminated intravascular coagulation, hemophagocytic lymphohistiocytosis, tocilizumab, corticosteroids, blood-brain barrier integrity, encephalopathy, cytokine-targeted therapy, immunotherapy toxicity management
MeSH terms
Cytokine Release Syndrome, Interleukin-6 Inhibitors, Adrenal Cortex Hormones, Humans, Interleukin-6, Immunotherapy, Adoptive, Hematologic Neoplasms, Cancer Vaccines, Neurotoxicity Syndromes, Antibodies, Monoclonal, Humanized, Drug-Related Side Effects and Adverse Reactions

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