Ipilimumab

Mechanism :

Ipilimumab is a recombinant human IgG1 immunoglobulin monoclonal antibody that binds to the cytotoxic T-lymphocyte associated antigen 4 (CTLA-4). CTLA-4 is a down-regulator of T-cell activation pathways.

Indication :

Metastatic colorectal cancer
Unresectable or metastatic melanoma
Advanced renal cell carcinoma

Contraindications :

Hypersensitivity to ipilimumab or any component of the formulation; active life-threatening autoimmune disease, or with organ transplantation graft where further immune activation is potentially imminently life-threatening.

Dosing :

Use in children ≥12 years of age and adolescents.

Metastatic colorectal cancer:

1 mg/kg IV once every 3 weeks (in combination with nivolumab) for up to 4 combination doses.

Unresectable or metastatic melanoma:

3 mg/kg IV every 3 weeks for a maximum of 4 doses; doses may be delayed due to toxicity, but all doses must be administered within 16 weeks of the initial dose.

Adverse Effect :

Fatigue, headache, skin rash, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis, dermal ulceration, necrotic, bullous or hemorrhagic dermatitis, weight loss, diarrhea, nausea, increased serum lipase and amylase, vomiting, colitis, abdominal pain, anemia, increased serum AST,ALT, alkaline phosphatase, cough, dyspnea, fever, pituitary insufficiency.

Interaction :

Vemurafenib: Ipilimumab may enhance the hepatotoxic effect of Vemurafenib.
Discontinue breastfeeding during treatment and for 3 months following the final dose.

Hepatic Dose :

Baseline Hepatic Impairment
Mild hepatic impairment: No dosage adjustment is required.
Moderate to severe hepatic impairment: Specific guidelines for dosage adjustment are not available.

Impairment during treatment:
AST or ALT >2.5 to =5 upper limit of normal (ULN) or bilirubin >1.5 to =3 ULN: Temporarily withhold treatment. If hepatotoxicity resolves to grade 0 or 1 in less than 6 weeks and the patient is receiving less than prednisone 7.5 mg/day (or equivalent), resume therapy. If the hepatotoxicity lasts longer than 6 weeks or if the dose of corticosteroid cannot be reduced to the equivalent of prednisone 7.5 mg/day, permanently discontinue therapy.
ALT or AST >5 times ULN, or total bilirubin >3 times ULN: Permanently discontinue; also administer systemic corticosteroids (prednisone 1 to 2 mg/kg/day or equivalent). May begin tapering corticosteroid (over 1 month) when LFTs show sustained improvement or return to baseline.