Pembrolizumab

Mechanism :

Pembrolizumab is a highly selective anti-PD-1 humanized monoclonal antibody which inhibits programmed cell death-1 (PD-1) activity by binding to the PD-1 receptor on T-cells to block PD-1 ligands (PD-L1 and PD-L2) from binding.

Indication :

Relapsed or refractory Hodgkin’s lymphoma, primary mediastinal large B-cell lymphoma
Recurrent or metastatic cervical cancer, gastric cancer, head and neck cancer.
Unresectable or metastatic melanoma, microsatellite instability-high cancer, urothelial carcinoma.

Contraindications :

Hypersensitivity to pembrolizumab or any component of the formulation.

Dosing :

Relapsed or refractory Hodgkin’s lymphoma, primary mediastinal large B-cell lymphoma; unresectable or metastatic microsatellite instability-high cancer:

≥2 years:

2 mg/kg IV (Maximum: 200 mg) once every 3 weeks until disease progression or unacceptable toxicity. Duration: Up to 24 months.

Adverse Effect :

Peripheral edema, fatigue, headache, pruritus, skin rash, hyperglycemia, hypoalbuminemia, hyponatremia, hypertriglyceridemia, hypophosphatemia, anorexia, nausea, constipation, UTI, anemia, lymphocytosis, thrombocytopenia, increased serum ALP, AST, ALT, creatinine, musculoskeletal pain, cough, dyspnea, fever.

Interaction :

Thalidomide Analogues: Pembrolizumab may enhance the adverse/toxic effect of Thalidomide Analogues.

Hepatic Dose :

For existing hepatic impairment:
Mild hepatic impairment: dose adjustment is not required.
Moderate hepatic impairment: Dose adjustment guidelines are not available, as dosing has not been studied.
Severe hepatic impairment: Permanently discontinue pembrolizumab therapy.
Gastrointestinal bleeding suggestive of portal hypertension: Permanently discontinue pembrolizumab therapy.
New onset of clinically detectable ascites, or encephalopathy: Permanently discontinue pembrolizumab therapy.

Immune-mediated hepatitis in patients WITHOUT hepatocellular cancer
AST/ALT 3.1 to 5 times the upper limit of normal (ULN) or a total bilirubin level 1.6 to 3 times the ULN: Withhold pembrolizumab therapy and administer prednisolone (initial dose of 0.5 to 1 mg/kg/day followed by tapering). Restart therapy when liver injury is grade 1 or less. Permanently discontinue therapy if there is no recovery within 12 weeks.
AST/ALT greater than 5 times the ULN or a total bilirubin level greater than 3 times the ULN: Permanently discontinue therapy. Give prednisolone 1 to 2 mg/kg/day, followed by tapering.
Liver metastases and grade 2 AST/ALT elevations at baseline, with AST/ALT increases of greater than or equal to 50% relative to baseline lasting at least 1 week: Permanently discontinue pembrolizumab therapy.

Immune-mediated hepatitis in patients WITH hepatocellular cancer
If baseline AST/ALT was less than 2 times ULN and AST/ALT increases to greater than or equal to 5 times ULN: Withhold pembrolizumab therapy and administer corticosteroids. Resume treatment when AST or ALT recovers to grade 1 or less, or to baseline.
If baseline AST/ALT was greater than or equal to 2 times ULN and AST/ALT increases to greater than 3 times baseline: Withhold pembrolizumab therapy and administer corticosteroids. Resume treatment when AST or ALT recovers to grade 1 or less, or to baseline.
AST/ALT greater than 10 times ULN regardless of baseline: Permanently discontinue pembrolizumab therapy.
Total bilirubin greater than 2 mg/dL if baseline was less than 1.5 mg/dL OR total bilirubin greater than 3 mg/dL regardless of baseline: Hold pembrolizumab therapy and administer corticosteroids. Resume treatment when total bilirubin recovers to grade 1 or less, or to baseline.