Cytokine Release Syndrome (CRS)

What is cytokine release syndrome (CRS)? Cytokine release syndrome is an adverse event that can occur after treatment with certain immunotherapies, such as chimeric antigen receptor (CAR)-T cell therapy, therapeutic antibodies, and haploidentical allogeneic transplantation, which cause a sudden release of a large number of cytokines from the affected cells. Symptoms of CRS can range from mild fever, nausea, and headache, to life threatening organ dysfunction.

How is CRS graded?

CRS grading is used to monitor the severity of symptoms for those receiving immunotherapy for cancer. Historically, there have been several scales that were being used by multiple institutions. However, a consensus grading has since been created.

  • Grade 1 CRS is defined as a fever that is not attributable to another cause. The fever may be accompanied by constitutional symptoms such as fever, headache, fatigue, nausea, myalgia, and malaise.
  • Grade 2 CRS is characterized by fever accompanied by hypotension that is responsive to fluids and/or hypoxia that requires supplemental oxygen through low-flow nasal cannula or blow-by. 
  • Grade 3 CRS is describes as fever with hypotension that requires one vasopressor and/or hypoxia that requires supplemental oxygen delivery through high-flow nasal cannula, facemask, nonrebreather mask, or Venturi mask.

Source: Lee et al. (2019). ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biology of Blood and Marrow Transplantation, 25(4), 625–638.