Management of cytokine release syndrome related to CAR-T cell therapy

Front Med. 2019 Oct;13(5):610-617. doi: 10.1007/s11684-019-0714-8. Epub 2019 Sep 28.

Abstract

Chimeric antigen receptor T (CAR-T) cell therapy is a novel cellular immunotherapy that is widely used to treat hematological malignancies, including acute leukemia, lymphoma, and multiple myeloma. Despite its remarkable clinical effects, this therapy has side effects that cannot be underestimated. Cytokine release syndrome (CRS) is one of the most clinically important and potentially life-threatening toxicities. This syndrome is a systemic immune storm that involves the mass cytokines releasing by activated immune cells. This phenomenon causes multisystem damages and sometimes even death. In this study, we reported the management of a patient with recurrent and refractory multiple myeloma and three patients with acute lymphocytic leukemia who suffered CRS during CAR-T treatment. The early application of tocilizumab, an anti-IL-6 receptor antibody, according to toxicity grading and clinical manifestation is recommended especially for patients who suffer continuous hyperpyrexia, hypotensive shock, acute respiratory failure, and whose CRS toxicities deteriorated rapidly. Moreover, low doses of dexamethasone (5-10 mg/day) were used for refractory CRS not responding to tocilizumab. The effective management of the toxicities associated with CRS will bring additional survival opportunities and improve the quality of life for patients with cancer.

Keywords: chimeric antigen receptor T cell; cytokine release syndrome; tocilizumab.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Cytokine Release Syndrome / drug therapy*
  • Cytokine Release Syndrome / etiology
  • Cytokines / immunology
  • Dexamethasone / therapeutic use*
  • Humans
  • Immunotherapy, Adoptive / adverse effects*
  • Male
  • Middle Aged
  • Multiple Myeloma / complications
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / complications
  • Quality of Life
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Chimeric Antigen / immunology*
  • Young Adult

Substances

  • Antibodies, Monoclonal, Humanized
  • Cytokines
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen
  • Dexamethasone
  • tocilizumab