A Concise Review of Neurologic Complications Associated with Chimeric Antigen Receptor T-cell Immunotherapy

Michael W Ruff¹, Elizabeth L Siegler², Saad S Kenderian³

Affiliations

¹ T Cell Engineering, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA; Department of Neurology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA.
² T Cell Engineering, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA; Division of Hematology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA.
³ T Cell Engineering, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA; Division of Hematology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA; Department of Molecular Medicine, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA; Department of Immunology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA. Electronic address: Kenderian.saad@mayo.edu.

PMID: 33040871
DOI: 10.1016/j.ncl.2020.08.001

Review

A Concise Review of Neurologic Complications Associated with Chimeric Antigen Receptor T-cell Immunotherapy

Michael W Ruff et al. Neurol Clin. 2020 Nov.

. 2020 Nov;38(4):953-963.

doi: 10.1016/j.ncl.2020.08.001. Epub 2020 Sep 12.

Authors

Michael W Ruff¹, Elizabeth L Siegler², Saad S Kenderian³

Affiliations

¹ T Cell Engineering, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA; Department of Neurology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA.
² T Cell Engineering, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA; Division of Hematology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA.
³ T Cell Engineering, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA; Division of Hematology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA; Department of Molecular Medicine, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA; Department of Immunology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA. Electronic address: Kenderian.saad@mayo.edu.

PMID: 33040871
DOI: 10.1016/j.ncl.2020.08.001

Abstract

Chimeric antigen receptor-engineered T (CAR-T) cell immunotherapy has been successful in treating many types of hematological malignancies. CAR-T therapy, however, has been associated with toxicities, including cytokine release syndrome (CRS) as well as immune effector cell-associated neurotoxicity syndrome (ICANS). ICANS presentation is variable, largely reversible, and manifests with encephalopathy and focal neurologic deficits. Treatment strategies largely are supportive. ICANS pathophysiology likely is related to that of CRS. Preclinical studies and clinical experience have shed light on the driving forces of ICANS and have yielded new strategies to mitigate ICANS occurrence.

Keywords: Axicabtagene ciloleucel; CAR-T; Chimeric antigen receptor; Neurotoxicity; Tisagenlecleucel.

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Conflict of interest statement

Disclosure S.S. Kenderian is an inventor on patents in the field of CAR immunotherapy that are licensed to Novartis (through an agreement between Mayo Clinic, University of Pennsylvania, and Novartis), Humanigen (through Mayo Clinic), and Mettaforge (through Mayo Clinic). S.S. Kenderian receives research funding from Kite, Gilead, Juno, Celgene, Novartis, Humanigen, MorphoSys, Tolero, Sunesis, and Lentigen. S.S. Kenderian has participated in advisory boards with Humanigen, Kite, and Juno.

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A Concise Review of Neurologic Complications Associated with Chimeric Antigen Receptor T-cell Immunotherapy

Affiliations

A Concise Review of Neurologic Complications Associated with Chimeric Antigen Receptor T-cell Immunotherapy

Authors

Affiliations

Abstract

Conflict of interest statement

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