Modified protocol for assessing and managing cytokine-related toxicities after CAR T-cell therapy at the Samsung Medical Center based on the ASTCT and ASCO guidelines
Toxicity | Grade 1 | Grade 2 | Grade 3 | Grade 4 | |
---|---|---|---|---|---|
CRS | Fever | Temperature ≥38°C | Temperature ≥38°C | Temperature ≥38°C | Temperature ≥38°C |
Hypotension | None | Not requiring vasopressors | Requiring one vasopressor±vasopressin | Life-threatening hypotension requiring multiple vasopressors | |
Hypoxia | None | Requiring low-flow nasal cannula (≤6 L/min) | Requiring high-flow nasal cannula (>6 L/min), facemask, or venturi mask | Requiring positive pressure (e.g., CPAP, BiPAP, mechanical ventilation) | |
Tocilizumab IV administration (8 mg/kg) |
Consider tocilizumab for fever not attributable to any other cause in a patient with high tumor burden or elderly frail status | Repeat tocilizumab every 8 hrs; limit to a maximum of three doses in a 24-hr period | Repeat tocilizumab every 8 hrs; limit to a maximum of three doses in a 24-hr period | Repeat tocilizumab every 8 hrs; limit to a maximum of three doses in a 24-hr period | |
Steroid | None | Consider dexamethasone 10 mg IV every 12 or 24 hrs if no improvement within 24 hrs of starting tocilizumab | Dexamethasone 10 mg IV every 6 or 12 hrs and taper based on symptoms | Methylprednisolone 1 g per day IV for 3 days followed by 250 mg every 12 hrs for 2 days and slow tapering | |
Supportive care | Antipyretics, IV hydration, empiric broad-spectrum antibiotics, GCSF, and symptomatic treatment | Supportive treatment as per grade 1 Consider ICU care |
Supportive treatment as per grade 2 at ICU with intensive treatments for organ toxicities (e.g., mechanical ventilation as needed) | Supportive treatment as per grade 3 at ICU with intensive treatments for organ toxicities (e.g., mechanical ventilation as needed) | |
ICANS | Consciousness | Alert | Awaken to voice | Awaken to painful stimuli | Unarousable |
ICE test | ICE score 7–9 | ICE score 3–6 | ICE score 0–2 | ICE score 0 | |
Management | Supportive care | Dexamethasone 10 mg IV; if no improvement, dexamethasone 10 mg IV every 6–12 hrs If CRS +, consider tocilizumab as per CRS grade 2 |
Dexamethasone 10 mg IV every 6 hrs or methylprednisolone 1 mg/kg IV every 12 hrs If CRS +, consider tocilizumab as per CRS grade 3 and ICU care |
Same as CRS grade 4 at ICU with supportive treatments for organ toxicities |
Abbreviations: ASCO, American Society of Clinical Oncology; ASTCT, American Society for Transplantation and Cellular Therapy; BiPAP, bilevel positive airway pressure; CAR, chimeric antigen receptor; CPAP, continuous positive airway pressure; CRS, cytokine release syndrome; GCSF, granulocyte colony-stimulating factor; ICANS, immune effector cell-associated neurotoxicity syndrome; ICE, immune effector cell-associated encephalopathy; ICU, intensive care unit; IV, intravenous.
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