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CNS Drugs

, Volume 32, Issue 12, pp 1091–1101 | Cite as

Neurotoxicity Associated with CD19-Targeted CAR-T Cell Therapies

  • Juliane Gust
  • Agne Taraseviciute
  • Cameron J. Turtle
Leading Article

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.

Notes

Compliance with Ethical Standards

Funding

No external funding was used in the preparation of this article.

Conflict of interest

Cameron J. Turtle receives research funding from Juno Therapeutics/Celgene and Nektar Therapeutics; has served on advisory boards for Juno Therapeutics/Celgene, Nektar Therapeutics, Precision Biosciences, Caribou Biosciences, Eureka Therapeutics, Gilead, and Aptevo; and has options in Precision Biosciences, Eureka Therapeutics and Caribou Biosciences. Juliane Gust and Agne Taraseviciute have no conflicts of interest that are directly relevant to the contents of this article.

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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Juliane Gust
    • 1
    • 2
  • Agne Taraseviciute
    • 3
  • Cameron J. Turtle
    • 4
    • 5
  1. 1.Center for Integrative Brain ResearchSeattle Children’s Research InstituteSeattleUSA
  2. 2.Division of Pediatric Neurology, Department of NeurologyUniversity of WashingtonSeattleUSA
  3. 3.Department of PediatricsUniversity of Southern CaliforniaLos AngelesUSA
  4. 4.Clinical Research Division and Integrated Immunotherapy Research CenterFred Hutchinson Cancer Research CenterSeattleUSA
  5. 5.Department of MedicineUniversity of WashingtonSeattleUSA

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