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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Cytokine Release Syndrome / drug therapy*
  • Cytokine Release Syndrome / immunology
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Chimeric Antigen / immunology*
  • Receptors, Interleukin-6 / antagonists & inhibitors
  • Receptors, Interleukin-6 / immunology
  • Treatment Outcome


  • Antibodies, Monoclonal, Humanized
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen
  • Receptors, Interleukin-6
  • tocilizumab