Insights into cytokine release syndrome and neurotoxicity after CD19-specific CAR-T cell therapy

Curr Res Transl Med. 2018 May;66(2):50-52. doi: 10.1016/j.retram.2018.03.003. Epub 2018 Apr 3.

Abstract

T-cells engineered to express CD19-specific chimeric antigen receptors (CD19 CAR-T cells) can achieve high response rates in patients with refractory/relapsed (R/R) CD19+ hematologic malignancies. Nonetheless, the efficacy of CD19-specific CAR-T cell therapy can be offset by significant toxicities, such as cytokine release syndrome (CRS) and neurotoxicity. In this report of our presentation at the 2018 Second French International Symposium on CAR-T cells (CAR-T day), we describe the clinical presentations of CRS and neurotoxicity in a cohort of 133 adults treated with CD19 CAR-T cells at the Fred Hutchinson Cancer Research Center, and provide insights into the mechanisms contributing to these toxicities.

Keywords: Adoptive t-cell therapy; Chimeric antigen receptor therapy; Cytokine release syndrome; Hematological malignancies; Neurotoxicity; Review.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Antigens, CD19 / physiology
  • Cytokines / metabolism*
  • Cytokines / toxicity*
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / pathology
  • Hematologic Neoplasms / therapy
  • Humans
  • Immunotherapy, Adoptive / adverse effects*
  • Immunotherapy, Adoptive / methods
  • Neurotoxicity Syndromes / etiology*
  • Receptors, Antigen, T-Cell / physiology
  • Receptors, Antigen, T-Cell / therapeutic use*
  • T-Lymphocytes / physiology*
  • T-Lymphocytes / transplantation
  • Treatment Outcome

Substances

  • Antigens, CD19
  • CD19-specific chimeric antigen receptor
  • Cytokines
  • Receptors, Antigen, T-Cell