Neurotoxicity Associated with CD19-Targeted CAR-T Cell Therapies

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


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.

Publication types

  • Review

MeSH terms

  • Antigens, CD19 / metabolism*
  • Cytokines / blood
  • Cytokines / cerebrospinal fluid
  • Humans
  • Immunologic Factors / therapeutic use
  • Immunotherapy, Adoptive / methods*
  • Neurotoxicity Syndromes / epidemiology
  • Neurotoxicity Syndromes / immunology*
  • Neurotoxicity Syndromes / metabolism
  • Neurotoxicity Syndromes / therapy*
  • Receptors, Antigen, T-Cell / metabolism*


  • Antigens, CD19
  • Cytokines
  • Immunologic Factors
  • Receptors, Antigen, T-Cell