Usual Adult Dose for Malignant Melanoma

20 mcg IV on Day 1, 30 mcg IV on Day 8, 68 mcg IV on Day 15, and then 68 mcg IV once a week thereafter
Duration of therapy: Until unacceptable toxicity or disease progression occur

Comments:

• Patient selection should be based on a positive human leukocyte antigen-A*02:01 (HLA-A*02:01) genotyping test.
• A US FDA-approved test for the detection of HLA-A*02:01 genotyping is not currently available.

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Dose Adjustments

No dosage reduction is recommended for this drug; the following dosage modifications are recommended for adverse reactions.

CYTOKINE RELEASE SYNDROME (CRS):

• MODERATE defined as temperature at least 38C (100.4F) with hypotension that responds to fluids (does not require vasopressors) OR hypoxia requiring low flow nasal canula (up to 6 L/min) or blow-by oxygen:
• If hypotension and hypoxia do not improve within 3 hours or CRS worsens, care should be escalated and signs/symptoms should be managed according to next higher level of severity.
• For moderate CRS that is persistent (lasting 2 to 3 hours) or recurrent, corticosteroid premedication (e.g., dexamethasone 4 mg or equivalent) should be administered at least 30 minutes before the next dose.
• SEVERE defined as temperature at least 38C with hemodynamic instability requiring a vasopressor (with or without vasopressin) OR worsening hypoxia or respiratory distress requiring high flow nasal canula (greater than 6 L/min oxygen) or face mask:
• This drug should be withheld until CRS and sequelae have resolved.
• IV corticosteroid (e.g., 2 mg/kg/day methylprednisolone or equivalent) should be administered.
• This drug should resume at the same dose level (i.e., should not escalate if severe CRS occurred during initial dose escalation; escalation should resume once dosage is tolerated).
• For severe CRS, corticosteroid premedication (e.g., dexamethasone 4 mg or equivalent) should be administered at least 30 minutes before the next dose.
• LIFE-THREATENING defined as temperature at least 38C with hemodynamic instability requiring multiple vasopressors (excluding vasopressin) OR worsening hypoxia or respiratory distress despite oxygen administration requiring positive pressure:
• This drug should be permanently discontinued.
• IV corticosteroid (e.g., 2 mg/kg/day methylprednisolone or equivalent) should be administered.

• Grade 2 or 3:
• This drug should be withheld until grade 1 or lower or baseline.
• This drug should resume at same dose level (i.e., should not escalate if grade 3 skin reactions occurred during initial dose escalation; escalation should resume once dosage is tolerated).
• For persistent reactions not responding to oral steroids, IV corticosteroid (e.g., 2 mg/kg/day methylprednisolone or equivalent) should be considered.
• Grade 4:
• This drug should be permanently discontinued.
• IV corticosteroid (e.g., 2 mg/kg/day methylprednisolone or equivalent) should be administered.

• Grade 3 or 4:
• This drug should be withheld until grade 1 or lower or baseline.
• This drug should resume at same dose level if the elevated liver enzymes occur in the setting of grade 3 CRS; escalation should resume if next administration is tolerated.
• If the elevated liver enzymes occur outside the setting of grade 3 CRS, escalation should resume if the current dose is less than 68 mcg, or this drug should resume at same dose level if escalation has completed.
• IV corticosteroids should be administered if no improvement within 24 hours.

• Grade 3:
• This drug should be withheld until grade 1 or lower or baseline.
• This drug should resume at same dose level (i.e., should not escalate if other grade 3 adverse reaction occurred during initial dose escalation; escalation should resume once dosage is tolerated).
• Grade 4:
• This drug should be permanently discontinued.

Precautions

US BOXED WARNING:

• CYTOKINE RELEASE SYNDROME (CRS): CRS, which may be serious or life-threatening, occurred in patients receiving this drug; patients should be monitored for at least 16 hours after the first 3 infusions and then as clinically indicated.

Dialysis

Data not available

Other Comments

Administration advice:

• Administer the first 3 infusions in an appropriate health care setting; monitor patients during the infusion and for at least 16 hours after the infusion is complete.
• If the patient does not have grade 2 or worse hypotension (requiring medical intervention) during or after the third infusion, administer subsequent doses in an appropriate ambulatory care setting; monitor patients for at least 30 minutes after each of these infusions.
• Administer the diluted solution immediately via IV infusion over 15 to 20 minutes through a dedicated IV line.
• Use a sterile, nonpyrogenic, low protein binding 0.2 micron in-line filter infusion set.
• Administer the entire contents of the infusion bag.
• Do not mix this drug with other drugs or administer other drugs through the same IV line.
• After infusion is complete, flush the infusion line with adequate volume of sterile 0.9% Sodium Chloride Injection, USP to ensure the entire contents of the infusion bag have been administered.

• Vial: Store in original carton refrigerated at 2C to 8C (36F to 46F) and protect from light until time of use; do not freeze or shake.
• Prepared infusion bag: Administer within 4 hours from time of preparation (including duration of infusion); during the 4-hour window, keep the infusion bag at room temperature. If not used immediately, store in a refrigerator at 2C to 8C (36F to 46F) and infuse within 24 hours from time of preparation (includes storage time in refrigerator, time to equilibrate to room temperature, and duration of infusion).
• Once removed from refrigerator, do not refrigerate again; do not freeze.
• Discard unused solution beyond the recommended storage time.

• A 2-step dilution process is required to prepare the final dose for infusion.
• The manufacturer product information should be consulted.

• Compatible: Albumin (Human); 0.9% Sodium Chloride Injection, USP
• This drug should not be mixed with other drugs.

• Dermatologic: For skin reactions
• Hepatic: ALT, AST, and total blood bilirubin (before starting and during therapy)
• Immunologic: For signs/symptoms of CRS (after administration)
• Investigations: Fluid status, vital signs, oxygenation level

• Read the US FDA-approved patient labeling (Patient Information).
• Immediately contact health care provider if signs/symptoms associated with CRS (e.g., pyrexia, hypotension, hypoxia, chills, nausea, vomiting, fatigue, headache) occur.
• Contact health care provider if signs/symptoms of progressive/intolerable skin reactions develop.
• Contact health care provider if signs/symptoms of liver toxicity (e.g., right-sided abdominal pain, jaundice, scleral icterus) develops.
• Patients of childbearing potential: Notify health care provider if you are pregnant or become pregnant; use effective contraception while receiving this drug and for 1 week after the last dose.
• Do not breastfeed during therapy and for 1 week after the last dose.