Chimeric Antigen Receptor T Cell-Related Neurotoxicity

Mechanisms, Clinical Presentation, and Approach to Treatment

Jessica Rice, Sarah Nagel, Julie Randall, Holly Hinson

Research output: Contribution to journalReview article

Abstract

Purpose of review: Chimeric antigen receptor T cell (CAR-T) adoptive cell therapy is an effective treatment for patients with refractory B cell malignancies. As its use has grown, there has been an increase in the incidence of a serious, potentially fatal neurotoxicity known as immune effector cell-associated neurotoxicity syndrome (ICANS). This review discusses the clinical manifestations of this neurotoxicity syndrome, current grading systems, management strategies, and proposed biologic mechanisms leading to neurotoxicity. Recent findings: Current research suggests that patients with a higher disease burden and higher CAR-T cell doses are positively associated with the development of ICANS, as are elevated serum levels of proinflammatory cytokines and the presence of cytokine release syndrome (CRS). While patterns observed on neuroimaging and electroencephalogram (EEG) are non-specific for the diagnosis of ICANS, each modality may provide helpful clinical information such as the detection of cerebral edema, the most serious of associated symptoms. Anti-epileptic medications and corticosteroids may ameliorate the symptoms of ICANS. Summary: The mechanism for ICANS is currently unknown; however, systemic inflammation and cytokine production triggering a cascade of endothelial activation and BBB disruption likely contribute. With limited treatment options available, further clinical research into the precise mechanism and treatment is urgently needed as the use of CAR-T and other adoptive cell therapies continues to grow.

Original languageEnglish (US)
Article number40
JournalCurrent Treatment Options in Neurology
Volume21
Issue number8
DOIs
StatePublished - Aug 1 2019

Fingerprint

Neurotoxicity Syndromes
T-Cell Antigen Receptor
Cytokines
Cell- and Tissue-Based Therapy
Therapeutics
Brain Edema
Research
Neuroimaging
Electroencephalography
Adrenal Cortex Hormones
B-Lymphocytes
Inflammation
Incidence
Serum

Keywords

  • Adoptive cell transfer
  • Blood-brain barrier
  • Cerebral edema
  • Chimeric antigen receptor T cell
  • Immune effector cell-associated neurotoxicity syndrome

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Chimeric Antigen Receptor T Cell-Related Neurotoxicity : Mechanisms, Clinical Presentation, and Approach to Treatment. / Rice, Jessica; Nagel, Sarah; Randall, Julie; Hinson, Holly.

In: Current Treatment Options in Neurology, Vol. 21, No. 8, 40, 01.08.2019.

Research output: Contribution to journalReview article

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