Assessment and management of cytokine release syndrome and neurotoxicity following CD19 CAR-T cell therapy

Expert Opin Biol Ther. 2020 Jun;20(6):653-664. doi: 10.1080/14712598.2020.1729735. Epub 2020 Feb 24.

Abstract

Introduction: The success of CD19 chimeric antigen receptor (CAR)-T cell therapy for treatment of CD19 positive malignancies has led to the FDA approval of two CD19 CAR-T cell products, tisagenlecleucel and axicabtagene ciloleucel, and ongoing clinical trials of new products. Cytokine release syndrome (CRS) and neurotoxicity are common toxicities associated with CD19 CAR-T cell therapies.Areas covered: This review will discuss CRS and neurotoxicity associated with CD19 CAR-T cell therapies, including clinical presentation, risk factors, pathophysiology, and therapeutic or prophylactic interventions.Expert opinion: In conjunction with improved understanding of the pathophysiology of CRS and neurotoxicity, we expect that the recent development of consensus guidelines for the evaluation of these toxicities will enhance management of patients undergoing CD19 CAR-T cell therapies.

Keywords: CAR-T cell; CD19 malignancies; chimeric antigen receptor; cytokine release syndrome; immunotherapy; leukemia; lymphoma; neurotoxicity.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antigens, CD19 / immunology*
  • Cytokine Release Syndrome / drug therapy
  • Cytokine Release Syndrome / etiology*
  • Humans
  • Immunotherapy, Adoptive / adverse effects*
  • Neurotoxicity Syndromes / drug therapy
  • Neurotoxicity Syndromes / etiology*
  • Risk Factors
  • Severity of Illness Index

Substances

  • Adrenal Cortex Hormones
  • Antibodies, Monoclonal, Humanized
  • Antigens, CD19
  • CD19 molecule, human
  • tocilizumab