Adjuvant ruxolitinib therapy relieves steroid-refractory cytokine-release syndrome without impairing chimeric antigen receptor-modified T-cell function

Immunotherapy. 2020 Oct;12(14):1047-1052. doi: 10.2217/imt-2020-0116. Epub 2020 Aug 11.

Abstract

Aim: Although numerous pro-inflammatory cytokines promote signaling via intracellular pathways involving Janus kinases, it remains unclear if ruxolitinib, a Janus kinase1/2 inhibitor, provides control of cytokine-release syndrome (CRS) without toxicity against therapeutic T cells. Materials & methods: We report successful clinical experience using ruxolitinib as adjuvant therapy to treat steroid-refractory CRS, which was related to CD22/CD19 chimeric antigen receptor-modified T cell sequential infusion, in a patient with Philadelphia chromosome-like acute lymphoblastic leukemia. Results: His symptoms improved rapidly after first dose of ruxolitinib; this was associated with reduced levels of circulating pro-inflammatory indicators. He eventually achieved minimal residual disease negative remission. Discussion: This is the first case in which ruxolitinib was used to treat steroid-refractory CRS; furthermore, this intervention had no apparent impact on the antileukemic actions of the chimeric antigen receptor-modified T cells. Our results suggest that adjuvant ruxolitinib therapy may be an alternative therapeutic approach for the management of CRS.

Keywords: CAR-T cells; CRS; ruxolitinib.

Publication types

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

MeSH terms

  • Adult
  • Combined Modality Therapy
  • Cytokine Release Syndrome / drug therapy*
  • Cytokine Release Syndrome / immunology
  • Glucocorticoids / therapeutic use
  • Humans
  • Immunotherapy / methods*
  • Male
  • Nitriles / therapeutic use*
  • Pyrazoles / therapeutic use*
  • Pyrimidines / therapeutic use*
  • Receptors, Chimeric Antigen / drug effects
  • Receptors, Chimeric Antigen / immunology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Treatment Outcome

Substances

  • Glucocorticoids
  • Nitriles
  • Pyrazoles
  • Pyrimidines
  • Receptors, Chimeric Antigen
  • ruxolitinib