Definition
- Monoclonal antibodies (mAbs) are engineered antibodies that target specific antigens on tumor cells or the tumor microenvironment.
- Can be naked, conjugated, or bispecific, depending on mechanism.
Classification by Mechanism
| Class | Examples | Mechanism / Target | Notes |
|---|---|---|---|
| Anti-CD20 | Rituximab, Obinutuzumab, Ofatumumab | B-cell depletion via ADCC, CDC, apoptosis | Used in CLL, NHL; risk of infusion reactions, HBV reactivation |
| Anti-CD52 | Alemtuzumab | Depletes lymphocytes (ADCC, CDC) | Used in CLL, T-PLL; profound immunosuppression |
| Anti-HER2 | Trastuzumab, Pertuzumab | Blocks HER2 signaling, ADCC | Breast cancer; monitor cardiac function |
| EGFR inhibitors | Cetuximab, Panitumumab | Inhibit EGFR signaling | Colorectal, head & neck cancers; rash, infusion reactions |
| VEGF/VEGFR inhibitors | Bevacizumab, Ramucirumab | Block angiogenesis | Solid tumors; hypertension, proteinuria, thrombosis |
| Immune checkpoint inhibitors | Nivolumab, Pembrolizumab, Atezolizumab, Durvalumab | Block PD-1/PD-L1 or CTLA-4 → T-cell activation | Wide range of solid tumors; immune-related AEs (colitis, hepatitis, endocrinopathies) |
| Conjugated mAbs | Brentuximab vedotin, Inotuzumab ozogamicin | Deliver cytotoxic payload to antigen-expressing cells | Watch for cytopenias, hepatotoxicity, neuropathy |
| Bispecific T-cell engagers (BiTEs) | Blinatumomab | Engage T-cells to kill CD19+ B-cells | Requires continuous IV infusion; risk of cytokine release syndrome |
General Toxicities of mAbs
- Infusion-related reactions (IRR) – fever, chills, hypotension, dyspnea (common with first infusion).
- Cytopenias – B/T-cell depletion (especially anti-CD20/anti-CD52).
- Immune-mediated toxicities – colitis, pneumonitis, hepatitis, endocrinopathies (checkpoint inhibitors).
- Organ-specific toxicity – cardiotoxicity (trastuzumab), nephrotoxicity (some conjugates).
- Infections – increased risk due to immunosuppression; prophylaxis may be indicated.
- Hypersensitivity reactions – anaphylaxis is rare but possible.
Monitoring
- Pre-infusion labs: CBC, liver function, renal function.
- During infusion: vital signs, symptoms of IRR.
- Post-infusion: ongoing monitoring for delayed reactions, cytopenias, organ toxicity.
- Disease-specific labs: e.g., cardiac function for trastuzumab, infection markers for anti-CD20 or anti-CD52 therapy.
Key Practical Points for Pharmacists
- Premedication is often required: acetaminophen, antihistamine, corticosteroid.
- Adjust infusion rate if infusion reaction occurs.
- Assess for drug interactions (e.g., chemotherapy combinations, immunosuppressants).
- Educate patients on delayed side effects, infection risk, and when to seek care.
- Ensure proper storage and handling – most mAbs require refrigeration and protection from light.
Summary:
Monoclonal antibodies are targeted therapies that either directly kill tumor cells, modulate immune response, or deliver cytotoxic payloads. Toxicities vary by target and mechanism, but infusion reactions, immunosuppression, and organ-specific effects are common themes.
Synonyms
mAbs