6
Management
Table 1. Cytokine Release Syndrome Recommendations
G3:
Fever:* temperature ≥38°C not
attributable to any other cause
Plus
Hypotension: requiring a
vasopressor with or without
vasopressin
And/or
Hypoxia: Requiring high-
flow nasal cannula, facemask,
nonrebreather mask, or Venturi
mask
• Continue supportive care as per G2 and include
vasopressors as needed.
• Admit patient to ICU.
• If echocardiogram was not already performed,
obtain ECHO to assess cardiac function and
conduct hemodynamic monitoring.
• Tocilizumab as per G2 if maximum dose.
not reached within 24-hour period plus
dexamethasone 10 mg IV every 6 hours (or
equivalent) and rapidly taper once symptoms
improve.
• If refractory, manage as per G4.
G4:
Fever:* temperature ≥38°C not
attributable to any other cause
Plus
Hypotension: requiring
multiple vasopressors (excluding
vasopressin)
And/or
Hypoxia: Requiring positive
pressure (e.g., CPAP, BiPAP,
intubation, and mechanical
ventilation)
• Continue supportive care as per G3 plus
mechanical ventilation as needed.
• Administer tocilizumab as per G2 if maximum
dose not reached within 24-hour period.
• Initiate high-dose methylprednisolone at a dose
of 500 mg IV every 12 hours for 3 days, followed
by 250 mg IV every 12 hours for 2 days, 125 mg
IV every 12 hours for 2 days, and 60 mg IV every
12 hours until CRS improvement to G1.
• If not improving, consider methylprednisolone
1,000 mg IV 2 times a day or alternate therapy.**
Additional considerations:
• Organ toxicities associated with CRS may be graded according to CTCAE v5.0 but
they do not influence CRS grading.
• CRS may be associated with cardiac, hepatic, and/or renal dysfunction.
• Earlier steroid use appears to reduce the rate of CAR T-cell treatment-related
CRS and neurologic events and is recommended for some products (axicabtagene
ciloleucel or bexucabtagene autoleucel).
• Strongly consider antifungal prophylaxis in patients receiving steroids for the
treatment of CRS and/or ICANS.
Footnotes:
* Fever is not required to grade subsequent CRS severity in patients who receive
antipyretics or anticytokine therapy (steroids or tocilizumab). Instead, CRS grading is
driven by hypotension and/or hypoxia.
** Noting limited experience with other agents, alternate options may include anakinra,
siltuximab, ruxolitinib, cyclophosphamide, and ATG.
(cont'd)
