Predictive Biomarkers For Cytokine Release Syndrome Cause By Immune Therapy (CAR T-Cells & Immune Cell Engagers)

Cytokine Release Syndrome

Cytokine Release Syndrome (CRS) is a supraphysiological response following any immune therapy that results in the activation or engagement of endogenous or infused T cells and or other immune effector cells. Symptoms can be progressive, must include fever at the onset, and may include hypotension, capillary leak, hypoxia, and end-organ dysfunction. 

Classification of CRS

Grade 1 CRS: Grade 1 CRS is defined as fever (> 38 degrees celsius) with or without constitutional symptoms of CRS include myalgia, arthralgia, and malaise with the coincidence of fever. 

Grade 2 CRS: Grade 2 CRS is defined as fever (>38 degrees celsius) with hypotension not requiring vasopressin and or hypoxia requiring the use of a low-flow nasal canula or blow-by.

Grade 3 CRS: Grade 3 CRS is defined as fever (>38 degrees celsius)  with hypotension requiring 1 vasopressor with or without vasopressin and hypoxia requiring high flow nasal cannula (>64 min), face mask, non-breather mask not attributable to any other cause. 

Grade 4 CRS: Grade 4 CRS is defined as fever (> 38-degree celsius) with hypotension requiring multiple vasopressors (excluding vasopressin) and or hypoxia requiring positive pressure not attributable to any other cause. As CRS progresses capillary leak often leads to pulmonary edema, impairment of ventilation in addition to oxygen.

Grade 5 CRS: By convention, grade 5 CRS is defined as death due to CRS with another cause is not the principal factor leading to this outcome.

Biomarkers Measured To Monitor Cytokine Release Syndrome

  • C-reactive protein
  • Ferritin
  • GM-CSF
  • Granzyme B
  • Intracellular Cell Adhesion Molecule 1 (ICAM-1)
  • Interleukin 2
  • Interleukin 6
  • Interleukin 5
  • Interleukin 8
  • Interleukin 10
  • Interleukin 13
  • Interleukin 18
  • Interleukin 2 receptor alpha
  • Interferon gamma
  • Macrophage Inflammatory Protein 1-alpha
  • Serum Amyloid A1 
  • Tumor Necrosis Factor-alpha
  • Fas L

Differential Cytokine Levels in CAR-T Cell Treatment

Breyanzi: Higher baseline markers in subject with CRS: CRP, Ferritin 

Differential Cytokine Levels in Bispecific Immune Cell Engagers

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