Cytokine Release Syndrome Management

CRS Classification and Grading

The American Society of Transplantation and Cellular Therapy (ASTCT) consensus grading system defines CRS as a "supraphysiologic response following immune therapy that results in the activation or engagement of endogenous or infused T cells and/or other immune effector cells" with grades defined as:

For Grade 1 CRS, the American Society of Clinical Oncology recommends supportive care with antipyretics, IV hydration, and symptom management 1
For Grade 1 CRS with prolonged symptoms or significant comorbidities, consider tocilizumab 8 mg/kg IV (not exceeding 800 mg) 2, 3
For Grade 2 CRS, the National Comprehensive Cancer Network recommends tocilizumab 8 mg/kg IV (not exceeding 800 mg), repeatable after 8 hours if no improvement 1, 2
For Grade 3 CRS, continue tocilizumab as in Grade 2 and add dexamethasone 10 mg IV every 6 hours 1, 3, 4, 5
For Grade 4 CRS, continue tocilizumab as in Grade 2 and add high-dose methylprednisolone: 500 mg IV every 12 hours for 3 days, followed by taper 1, 4, 5

For CRS refractory to tocilizumab and steroids, the American Society of Clinical Oncology recommends considering anakinra (IL-1 receptor antagonist) 1, 5
For CRS refractory to tocilizumab and steroids, the National Comprehensive Cancer Network recommends considering siltuximab (alternative IL-6 antagonist) 1, 5

The American Society of Clinical Oncology recommends laboratory monitoring, including CBC, CMP, magnesium, phosphorus, CRP, LDH, uric acid, fibrinogen, PT/PTT, and ferritin 1
The National Comprehensive Cancer Network recommends infection assessment, including blood and urine cultures, and chest radiograph if fever is present 1
The American Society of Clinical Oncology recommends cardiac monitoring, including continuous cardiac telemetry and pulse oximetry, for Grade 2+ CRS 1

The American Society of Clinical Oncology notes that fever is not required to grade subsequent CRS severity in patients receiving antipyretics or anticytokine therapy; instead, grading is based on hypotension and/or hypoxia 1, 2
The National Comprehensive Cancer Network recommends considering antifungal prophylaxis in patients receiving steroids for CRS 1, 2
The American Society of Clinical Oncology notes that earlier steroid use may reduce CAR T-cell treatment-related CRS and neurologic events for certain products 1
The American Society of Clinical Oncology notes that CRS may be associated with cardiac, hepatic, and/or renal dysfunction 1