Table 4. Tebentafusp Dosing Modification for Adverse Events.

Adverse reaction	Severity	Dosing modifications
Cytokine release syndrome	Moderate is defined as temperature ≥ 38oC with: Hypotension that responds to fluids (does not require vasopressors) or Hypoxia requiring low flow nasal cannula (≤ 6 L/min) or blow-by oxygen	If hypotension and hypoxia do not improve within 3 hours or CRS worsens, escalate care and manage according to the next high level of severity For moderate CRS that is persistent (lasting 2–3 hours) or recurrent, administer corticosteroid premedication (e.g., dexamethasone 4 mg or equivalent) at least 30 minutes prior to the next dose
	Severe is defined as temperature ≥ 38oC with: Hemodynamic instability requiring a vasopressor (with or without vasopressin) or Worsening hypoxia or respiratory distress requiring high flow nasal cannula (> 6 L/min oxygen) or face mask	Withhold until CRS and sequelae have resolved Administer intravenous corticosteroid (e.g., 2 mg/kg/day methylprednisolone or equivalent) Resume therapy at the same dose level (i.e., do not escalate if severe CRS occurred during initial dose escalation; resume escalation once dosage is tolerated) For severe CRS, administer corticosteroid premedication (e.g., dexamethasone 4 mg or equivalent) at least 30 minutes prior to the next dose
	Life-threatening is defined as temperature ≥ 38oC with: Hemodynamic instability requiring multiple vasopressors (excluding vasopressin) Worsening hypoxia or respiratory distress despite oxygen administration requiring positive pressure	Permanently discontinue Administer intravenous corticosteroid (e.g., 2 mg/kg/day methylprednisolone or equivalent)
Skin reactionsa	Grade 2 or 3	Withhold until ≤ grade 1 or baseline Resume at the same dose level (e.g., do not escalate if grade 3 skin reactions occurred during initial dose escalation; resume escalation once dosage is tolerated) For persistent reactions not responding to oral steroids, consider intravenous corticosteroid (e.g., 2 mg/kg/day methylprednisolone or equivalent)
	Grade 4	Permanently discontinue Administer intravenous corticosteroid (e.g., 2 mg/kg/day methylprednisolone or equivalent)
Elevated liver enzymesa	Grade 3 or 4	Withhold until ≤ grade 1 or baseline Resume at the same dose level if the elevated liver enzymes occur in the setting of grade 3 CRS; resume escalation if the next administration is tolerated If the elevated liver enzymes occur outside the setting of grade 3 CRS, resume escalation if the current dose is less than 68 micrograms, or resume at the same dose level if dose escalation has been completed Administer corticosteroids if no improvement within 24 hours
Other adverse reactionsa	Grade 3	Withhold until ≤ grade 1 or baseline Resume at the same dose level (i.e., do not escalate if other grade 3 adverse reactions occurred during initial dose escalation; resume escalation once the dosage is tolerated)
	Grade 4	Permanently discontinue

Note. CRS = cytokine release syndrome. Information from Immunocore Ltd. (2022).

^aGrading based on the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.