Kinetics and biomarkers of severe cytokine release syndrome after CD19 chimeric antigen receptor–modified T-cell therapy

Central memory T cells as independent predictors of CRS. Severe CRS was characterized by hemodynamic instability, capillary leak, and consumptive coagulopathy. Angiopoietin-2 and von Willebrand factor, which are biomarkers of endothelial activation, were increased during severe CRS and also before lymphodepletion in patients who subsequently developed CRS. We describe a classification-tree algorithm to guide studies of early intervention after CAR T-cell infusion for patients at high risk of severe CRS. These data provide a framework for early intervention studies to facilitate safer application of effective CD19 CAR T-cell therapy.

• NI
  National Institutes of Health

  Awards: P30 CA15704, CA136551, CA15704, R01 CA136551, DK56465
• JT
  Juno Therapeutics
• NC
  National Cancer Institute

  Awards: P30 CA15704, CA136551, CA15704
• NI
  National Institute of Diabetes and Digestive and Kidney Diseases

  Awards: DK56465, P30 CA15704, P30 DK56465, CA15704