Monoclonal antibody therapy

Mechanisms of action

• Target cell surface antigen
  • Blocks normal ligand binding
  • EGFR (epithelial growth factor receptor)
  • HER2
  • CD20 e.g. Rituximab -> Recruit immune system via Fc portion
• Target plasma proteins
  • TNF e.g. Adalimumab, infliximab
  • VEGF e.g. Benazizumab
• Checkpoints
  • CTLA4 checkpoint inhibitors block T cell suppression and increase T cell surveillance of tumor cells e.g. Ipilimumab, Trimelimumab
  • PD-1 checkpoint inhibitors block T cell suppression also and promote T cell surveillance for tumor cells e.g. Keytruda

Indications

• Haematological
• Solid tumors e.g. HER2 breast cancer, EGFR in NSCLC, Melanoma
• Rheumatoid arthritis e.g. Anti-TNFalpha if MTX fails
• Asthma e.g. Anti-IgE Omalizumab
• Osteoporosis e.g. Denosumab
• IBD e.g. Anti-TNFalpha often with immunomodulators (AZA/MTX)

Adverse events

• Infusion reactions
  • Usually within 1-2 hours
  • Range from mild to anaphylaxis
• Cytokine release syndrome
  • Severe immune reaction in response to immunotherapy
  • Usually lymphoid malignancy with subsequent positive feedback loop
  • Usually occur 2-3 days but up to 14 days from delivery
  • Fever, headache, nausea, malaise, hypotension, rash, chills, dyspnoea and tachycardia
  • DIC and transaminase rise can occur
  • More likely if high tumor load
• Immune-related adverse events
  • Dermatological – SJS
  • GI – Diarrhoea, colitis
  • Hepatic
  • Endocrine – Thyroiditis, hypophysitis, adrenal crisis
  • Renal – Nephritis
  • Ocular – Uveitis
  • Pulmonary toxicity – Pneumonitis
  • Myositis
• Grading
  • 1 – Manage supportively
  • 2 – Specific organ treatment, consider high-dose steroid
  • 3 – Severe. High-dose steroid methylprednisolone 1-2mg/kg/day
  • 4 – Life-threatening
    • Urgent high-dose steroid therapy, consider additional immunosuppressive therapies, targeted organ support

Last Updated on July 14, 2021 by Andrew Crofton