Management of Cytokine Release Syndrome (CRS) Due to CAR T-Cell Therapy

Initial Assessment and Monitoring

The American Society of Clinical Oncology recommends baseline laboratory evaluation before treatment, including complete blood count (CBC), comprehensive metabolic panel (CMP), magnesium, phosphorus, C-reactive protein (CRP), ferritin, LDH, uric acid, fibrinogen, PT/PTT for patients undergoing CAR T-cell therapy 1
Daily CRP and ferritin monitoring is recommended specifically for CRS surveillance in patients receiving CAR T-cell therapy 4
Assessing for infection with blood and urine cultures, chest radiograph if fever is present is crucial for patients undergoing CAR T-cell therapy 1

For grade 1 CRS, the American Society of Clinical Oncology recommends supportive care only, including antipyretics, IV hydration, and symptomatic management of organ toxicities 1, 2
For grade 2 CRS, the American Society of Clinical Oncology recommends tocilizumab 8 mg/kg IV as the primary intervention, with repeat doses every 8 hours if no improvement 1, 2
For grade 3 CRS, immediate ICU admission is required, with continuation of tocilizumab and addition of dexamethasone 10 mg IV every 6 hours 1, 2
For grade 4 CRS, aggressive intervention is required, including high-dose methylprednisolone 500 mg IV every 12 hours for 3 days, followed by tapering 1, 2

The American Society of Clinical Oncology recommends that fever is not required for grading subsequent CRS severity in patients receiving antipyretics or anticytokine therapy; grading is driven by hypotension and/or hypoxia 1, 2
Corticosteroids should not be routinely administered as pre-medication before CAR T-cell infusion, according to the American Society of Clinical Oncology 4
Antifungal prophylaxis should be strongly considered in patients receiving steroids for CRS and/or ICANS treatment, as recommended by the American Society of Clinical Oncology 1, 2

Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome should be suspected when ferritin >10,000 ng/ml, grade ≥3 organ toxicities, or evidence of hemophagocytosis in bone marrow is present, according to the American Society of Clinical Oncology 5
In the specific setting of grade 1 CRS with concurrent grade 2 ICANS, steroids (not tocilizumab) should be administered, as recommended by the European Society for Medical Oncology 7

Delaying tocilizumab administration should be avoided, as each 12-hour delay increases cardiotoxicity risk 1.7-fold, according to the European Society for Medical Oncology 7
GM-CSF should not be used, despite G-CSF being permissible, as recommended by the American Society of Clinical Oncology 1
Leukapheresis filters should not be used for CAR T-cell infusion, according to the American Society of Clinical Oncology 4