Pembrolizumab

• Mechanism of Action
• A monoclonal antibody directed against programmed cell death protein 1 (PD-1), a surface co-inhibitory receptor on circulating activated T cells, B cells and NK cells.
  PD-1 binds to two ligands (PD-L1 and PD-L2) and inhibit T cell receptor signalling, downregulating immune responses and promoting tolerance
  Many tumours express or overexpress PD-L1.
  Binding of anti-PD1 monoclonal antibodies to PD-1 leaves the ligand unable to bind, and therefore stimulates an ongoing immune response.

Clinical Use

• • Indication
  • Certain solid organ and haematologic malignancies with high levels of microsatellite instability (MSI). Malignancies of particular interest are melanoma, non-small cell lung cancer, renal cancer and bladder cancer, though this is a rapidly growing field.
• • Adverse Effects
  • Endocrinopathies - thyroiditis, adrenalitis, hypophysitis, diabetes mellitus
  • Pulmonary toxicity - pneumonitis
  • Hepatotoxicity - hepatitis, LFT derangement
  • GI toxicity - colitis
  • Rheumatological - flares of previous disease, PMR, arthralgias / myalgias
  • Skin - maculopapular rash, Stevens-Johnson syndrome, Sweet syndrome
  • Fatigue
  • Anorexia
  • Headache
  • Dizziness
  • Peripheral neuropathy
  • Nausea / vomiting / diarrhoea
  • Neutropaenia
  • Infections (particularly upper respiratory tract infection)