pembrolizumab

Pembrolizumab is a humanized monoclonal antibody that targets the programmed death-1 (PD-1) receptor. It is marketed as Keytruda and developed by Merck. By binding PD-1, pembrolizumab blocks its interaction with the ligands PD-L1 and PD-L2, thereby enhancing T-cell–mediated immune responses against tumor cells.

Mechanism and pharmacology: Pembrolizumab is an immune checkpoint inhibitor of the PD-1 pathway. It is typically given by intravenous infusion and acts to reinvigorate exhausted T cells within the tumor microenvironment. It is a IgG4-kappa antibody with a relatively long half-life, allowing dosing every few weeks in many regimens.

Indications and approvals: Pembrolizumab has been approved for numerous cancers, including unresectable or metastatic melanoma, metastatic non-small cell lung cancer, recurrent or metastatic head and neck squamous cell carcinoma, classical Hodgkin lymphoma, locally advanced or metastatic urothelial carcinoma, and certain gastric, cervical, and other cancers. It is also approved for tumors with high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR) and, in some settings, for tumors with PD-L1 expression. Dosing and schedule vary by indication and may include monotherapy or combination regimens with chemotherapy.

Administration and monitoring: Pembrolizumab is given as an intravenous infusion over about 30 minutes. Common regimens include 200 mg every 3 weeks or 400 mg every 6 weeks, with adjustments for certain indications. Before and during therapy, clinicians monitor for immune-related adverse events affecting the skin, gastrointestinal tract, liver, endocrine glands, lungs, and other organs. Management may involve temporary treatment interruption and corticosteroids or other immunosuppressants for severe events.

Adverse effects and safety: The most frequent side effects are fatigue, decreased appetite, rash, pruritus, and nausea. Serious immune-related events can occur and require prompt recognition and management. The safety profile varies by tumor type and combination therapy.