Table 2 Grading and management of CRS

Grade 1

Symptoms are not life threatening and require symptomatic treatment only

Fever, nausea, fatigue, headache, myalgias, malaise

Fever (≥ 38 °C)

For prolonged CRS (> 3 days) in patients with significant symptoms and/or comorbidities, consider tocilizumab as per Grade 2

N/A

Empiric broad-spectrum antibiotics, consider granulocyte colony-stimulating factor (G-CSF) if neutropenic

Maintenance IV fluids for hydration

Symptomatic management of organ toxicities

Grade 2

Symptoms require and respond to moderate intervention

Oxygen requirement < 40% or

Hypotension responsive to fluids or low dose of one vasopressor or

Grade 2 organ toxicity

Fever with hypotension not requiring vasopressors and/or

Hypoxia requiring low-flow nasal cannula or blow-by

Tocilizumab 8 mg/kg IV over 1 h (not to exceed 800 mg/dose)

Repeat in 8 h if no improvement; no more than 3 doses in 24 h, with a maximum of 4 doses total

For persistent refractory hypotension after 1–2 doses of anti-IL-6 therapy: Dexamethasone 10 mg IV every 6 h (or equivalent)

IV fluid bolus as needed

For persistent refractory hypotension after two fluid boluses and anti-IL-6 therapy: Start vasopressors, consider transfer to intensive care unit (ICU), consider echocardiogram, and initiate other methods of hemodynamic monitoring

Manage per Grade 3 if no improvement within 24 h after starting anti-IL-6 therapy

Symptomatic management of organ toxicities

Grade 3

Symptoms require and respond to aggressive intervention

Oxygen requirement ≥ 40% or

Hypotension requiring high dose^d or multiple vasopressors or

Grade 3 organ toxicity or grade 4 transaminitis

Fever with hypotension requiring a vasopressor with or without vasopressin and/or

Hypoxia requiring high-flow cannula, face mask, nonrebreather mask, or Venturi mask

Anti-IL-6 therapy as per Grade 2

if maximum dose not reached within 24 h period

Dexamethasone 10 mg IV every 6 h (or equivalent). If refractory, manage as grade 4

Transfer to ICU, obtain echocardiogram, and perform hemodynamic monitoring

Supplemental oxygen.

IV fluid bolus and vasopressors as needed

Symptomatic management of organ toxicities

Grade 4

Life-threatening symptoms

Requirement for ventilator support or

Grade 4 organ toxicity (excluding transaminitis)

Fever with hypotension requiring multiple vasopressors (excluding vasopressin) and/or

Hypoxia requiring positive pressure (eg, CPAP, BiPAP, intubation and mechanical ventilation)

Anti-IL-6 therapy as per Grade 2 if maximum dose not reached within 24 h period

Dexamethasone 10 mg IV every 6 h (or equivalent). If refractory, consider methylprednisolone 1000 mg/day IV

ICU care and hemodynamic monitoring

Mechanical ventilation as needed

IV fluid bolus and vasopressors as needed

Symptomatic management of organ toxicities