Active Ingredient: Retifanlimab
Retifanlimab is indicated as monotherapy for the first-line treatment of adult patients with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC) not amenable to curative surgery or radiation therapy.
For this indication, competent medicine agencies globally authorize below treatments:
For:
Intravenous, 500 milligrams retifanlimab, once every 4 weeks, over the duration of 2 years.
The recommended dose is 500 mg retifanlimab every 4 weeks administered as an intravenous infusion over 30 minutes. Treatment should continue until disease progression or unacceptable toxicity for up to 2 years.
Dose escalation or reduction of retifanlimab is not indicated. Recommended dose modifications to manage immune-related adverse reactions are provided in Table 1.
Table 1. Recommended dose modifications:
| Adverse reaction | Severitya | Dose modification |
|---|---|---|
| Pneumonitis | Grade 2 | Withhold until adverse reactions recover to Grades 0-1. |
| Grades 3 or 4 | Permanently discontinue. | |
| Colitis | Grades 2 or 3 | Withhold until adverse reactions recover to Grades 0-1. |
| Recurrent Grade 3 or Grade 4 | Permanently discontinue. | |
| Hepatitis with no tumour involvement of the liver OR Increased total bilirubin | Grade 3 with AST or ALT greater than 3 but no more than 8 times ULN OR TB increases to more than 1.5 and up to 3 times ULN | Withhold until adverse reactions recover to Grades 0-1. Permanently discontinue if no resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg/day (or equivalent) within 12 weeks of initiating steroids. |
| Grade 4 with AST or ALT increases to more than 8 times ULN OR TB greater than 3 times ULN | Permanently discontinue. | |
| Hepatitis with tumour involvement of the liver OR Increased total bilirubin | Grade 3 with AST or ALT more than 5 and up to 10 times ULN OR TB greater than 1.5 but no more than 3 times ULN | Withhold until adverse reactions recover to Grades 0-1. Permanently discontinue if no resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg/day (or equivalent) within 12 weeks of initiating steroids. |
| Grade 4 with AST or ALT increase to more than 10 times ULN OR TB greater than 3 times ULN | Permanently discontinue. | |
| Endocrinopathies • Adrenal insufficiency • Hypothyroidism • Hyperthyroidism • Type 1 diabetes mellitus • Hyperglycaemia • Hypophysitis | Grade 2 adrenal insufficiency | Withhold until adverse reactions recover to Grades 0-1 or otherwise clinically stable. |
| Grades 3 or 4 adrenal insufficiency | Withhold until adverse reactions recover to Grades 0-1. Permanently discontinue if no resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg/day (or equivalent) within 12 weeks of initiating steroids. | |
| Grades 3 or 4 hypothyroidism | Withhold until adverse reactions recover to Grades 0-1 or is otherwise clinically stable. | |
| Grades 3 or 4 hyperthyroidism | Withhold until adverse reactions recover to Grades 0-1 or is otherwise clinically stable. | |
| Grades 3 or 4 type 1 diabetes mellitus (or hyperglycaemia) | Withhold until adverse reactions recover to Grades 0-1 or is otherwise clinically stable. | |
| Grade 2 hypophysitis (asymptomatic) | Withhold until adverse reactions recover to Grades 0-1. May restart after controlled by hormone replacement therapy. | |
| Grade 2 hypophysitis (symptomatic e.g., headaches, visual disturbances) | Withhold until adverse reactions recover to Grades 0-1. May restart after controlled by hormone replacement therapy, if indicated and steroid taper is complete. | |
| Grade 3 or 4 hypophysitis (symptomatic) | Withhold until adverse reactions recover to Grades 0-1. Permanently discontinue if no resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg/day (or equivalent) within 12 weeks of initiating steroids. | |
| Nephritis with renal dysfunction | Grade 2 increased blood creatinine | Withhold until adverse reactions recover to Grades 0-1. |
| Grade 3 or 4 increased blood creatinine | Permanently discontinue.b | |
| Skin reactions | Grade 3 or suspected SJS or suspected TEN Persistent Grade 2 (≥ 2 weeks) | Withhold until adverse reactions recover to Grades 0-1. |
| Grade 4 or confirmed SJS or confirmed TEN | Permanently discontinue. | |
| Myocarditis | Confirmed Grades 2, 3 or 4 | Permanently discontinue. |
| Other immune-related adverse reactions (including myositis, encephalitis, demyelinating neuropathy, Guillain Barré syndrome, sarcoidosis, autoimmune haemolytic anaemia, pancreatitis, uveitis, diabetic ketoacidosis, arthralgia) | Grade 3 | Withhold until adverse reactions recover to Grades 0-1. |
| Grade 4 | Permanently discontinue. | |
| Persistent Grade 2 or 3 immune-related adverse reactions (excluding endocrinopathies) | Grade 2 or 3 (≥ 12 weeks after last dose) Recurrent Grade 3 or 4 Recurrent Grade 2 pneumonitis | Permanently discontinue. |
| Infusion-related reactions | Grade 1 | Interrupt or slow the rate of infusion. |
| Grade 2 | First occurrence: Interrupt infusion and resume at 50% of the original rate if symptoms resolve within 1 hour. Subsequent occurrences: Permanently discontinue after recommended prophylaxis. | |
| Grade 3 | Permanently discontinue. If rapidly responsive to symptomatic management and/or to brief interruption of infusion, retifanlimab does not need to be permanently discontinued. | |
| Grade 4 | Permanently discontinue. |
AST = aspartate aminotransferase; ALT = alanine aminotransferase; ULN = upper limit of normal; TB = total bilirubin; SJS = Stevens-Johnson syndrome; TEN = toxic epidermal necrolysis.
a Toxicity graded per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.
b Permanently discontinue only if retifanlimab is directly implicated in renal toxicity.
It must be administered by intravenous infusion over 30 minutes.
Retifanlimab must not be administered as an intravenous push or bolus injection.
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