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Review
. 2019 Aug;15(8):813-822.
doi: 10.1080/1744666X.2019.1629904. Epub 2019 Jun 20.

Tocilizumab for the treatment of chimeric antigen receptor T cell-induced cytokine release syndrome

Chelsea Kotch  1 , David Barrett  1 , David T Teachey  1
Affiliations
Review

Tocilizumab for the treatment of chimeric antigen receptor T cell-induced cytokine release syndrome

Chelsea Kotch et al. Expert Rev Clin Immunol. 2019 Aug.

Abstract

Introduction: Cancer-directed immunotherapies are transforming the landscape in oncology as new and exciting therapies move from the laboratory to the bedside. Chimeric antigen receptor T (CAR-T) cells are one of these novel therapies, demonstrating impressive efficacy against B-cell malignancies. With the development of new therapies, it is not uncommon to identify new and unanticipated toxicities. CAR-T cells cause unique toxicities not typically found with traditional cytotoxic chemotherapy or small molecule inhibitors. Areas covered: CAR-T cell associated toxicities include cytokine release syndrome (CRS) and CAR-T cell-related encephalopathy syndrome (CRES), alternatively known as immune effector cell-associated neurotoxicity syndrome (ICANS). Prompt identification and management of CRS and CRES are imperative for the prevention of life-threatening complications of these innovative therapies. This literature review describes the seminal trials of CD19-directed immunotherapy and the pathophysiology and management of the toxicities found with CAR-T cells. In addition, the use of the interleukin-6 receptor antibody tocilizumab for CRS is reviewed. Expert opinion: This review describes the recommended management of CRS and CRES and examines the current limitations in management. Alternative therapies for the treatment of CAR-T cell related toxicities are also explored. Furthermore, the review proposes future directions for research.

Keywords: Chimeric antigen receptor T cells (CAR T); chimeric antigen receptor T cell related encephalopathy syndrome (CRES); cytokine release syndrome (CRS); hemophagocytic lymphohistiocytosis (HLH); immune effector cell-associated neurotoxicity syndrome (ICANS); interleukin 6 (IL-6); neurotoxicity (NT); tisagenlecleucel; tocilizumab.

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Figure 1.
Figure 1.
Management of Chimeric Antigen Receptor T-Cell Cytokine Release Syndrome; Cytokine release syndrome CRS, Kilogram kg, Milligram mg
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