Cytokine Release Syndrome (CRS) Grading

Evaluates CRS severity in patients receiving immunotherapy for cancer.

Refer to the text below the tool for more information on the grading model.

Patients receiving immunotherapy for cancer are at risk of developing cytokine-mediated immunological reactions and multi-organ dysfunction and this CRS grading classifies the evidence in 5 independent grades and provides intervention advice where the case.

Interventions depending on CRS Grading (Lee et al.):

Grading	Intervention
Grade 1 CRS	Vigilant supportive care, assess for infection (treat fever and neutropenia if present; monitor fluid balance; give antipyretics/analgesics as needed)
Grade 2 CRS (no extensive comorbidities or older age)	Vigilant supportive care (monitor cardiac and other organ function closely)
Grade 2 CRS with extensive comorbidities or older age	Vigilant supportive care, tocilizumab with or without corticosteroids
Grade 3 CRS
Grade 4 CRS

Grading organ toxicity

Symptoms not life-threatening; only symptomatic treatment required (fever, nausea, fatigue, headache, myalgias, malaise)

Moderate intervention required for response: oxygen requirement <40%, hypotension responsive to fluids, low dose of one pressor, or grade 2 organ toxicity

Aggressive intervention required for response: oxygen requirement ≥40%, hypotension requiring high dose/multiple pressors, grade 3 organ toxicity, or grade 4 transaminitis

Life-threatening symptoms: ventilator required, or grade 4 organ toxicity (excluding transaminitis)

Death

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Cytokine Release Syndrome Grading

Oncological patients under immunological therapies have complicated ongoing processes and require specialized monitoring to prevent CRS, infection, tumor lysis syndrome organ toxicity and dysfunction.

Cytokine release syndrome (CRS) is a potentially life-threatening toxicity that has been observed following administration of natural and bispecific antibodies or following adoptive T-cell therapies in different oncological conditions.

CRS is associated with elevated circulating levels of several cytokines including interleukin (IL)-6 and interferon γ. Several studies (uncontrolled0 have shown that CRS can be reversed by immunosuppression using tocilizumab, an anti-IL-6 receptor antibody, with or without corticosteroids.

But early and aggressive immunosuppression could limit the efficacy of the immunotherapy so clinical gestalt is crucial at establishing where this administration is required to avoid life-threatening CRS.

Interventions depending on CRS Grading (Lee et al.):

Grading	Intervention
Grade 1 CRS	Vigilant supportive care, assess for infection (treat fever and neutropenia if present; monitor fluid balance; give antipyretics/analgesics as needed)
Grade 2 CRS (no extensive comorbidities or older age)	Vigilant supportive care (monitor cardiac and other organ function closely)
Grade 2 CRS with extensive comorbidities or older age	Vigilant supportive care, tocilizumab with or without corticosteroids
Grade 3 CRS
Grade 4 CRS