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Chimeric Antigen Receptor T Cell-Related Neurotoxicity: Mechanisms, Clinical Presentation, and Approach to Treatment

  • Critical Care Neurology (H Hinson, Section Editor)
  • Published:
Current Treatment Options in Neurology Aims and scope Submit manuscript

A Correction to this article was published on 09 August 2019

This article has been updated

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.

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Change history

  • 09 August 2019

    The correct spelling of the co-author should be listed as Sarah Nagle, MD.

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Authors and Affiliations

  1. Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, CR-127, Portland, OR, 97239, USA

    Jessica Rice MD & Holly E. Hinson MD MCR

  2. Department of Medicine, Oregon Health & Science University, Portland, OR, USA

    Sarah Nagle MD

  3. Portland State University, Portland, OR, USA

    Julie Randall BA

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Correspondence to Holly E. Hinson MD MCR.

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Holly E. Hinson has consulted for Biogen on an ischemic stroke study unrelated to the current work. All other authors declare that they have no conflicts of interest.

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The original version of this article was revised: The correct spelling of the co-author should be listed as Sarah Nagle, MD.

This article is part of the Topical Collection on Critical Care Neurology

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Rice, J., Nagle, S., Randall, J. et al. Chimeric Antigen Receptor T Cell-Related Neurotoxicity: Mechanisms, Clinical Presentation, and Approach to Treatment. Curr Treat Options Neurol 21, 40 (2019). https://doi.org/10.1007/s11940-019-0580-3

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