Definition
- Monoclonal antibodies targeting CD20, a surface antigen expressed on pre-B and mature B lymphocytes.
- Lead to B-cell depletion via multiple mechanisms.
Mechanism of Action
- Antibody-dependent cellular cytotoxicity (ADCC) – recruits NK cells/macrophages to kill B-cells.
- Complement-dependent cytotoxicity (CDC) – activates complement cascade → cell lysis.
- Direct apoptosis induction – binding to CD20 triggers programmed cell death in some cells.
Key Anti-CD20 Agents
| Drug | Type | Route | Indications | Notes / Toxicity |
|---|---|---|---|---|
| Rituximab | Chimeric (mouse/human) IgG1 | IV | NHL, CLL, autoimmune diseases | Infusion reactions, HBV reactivation, cytopenias |
| Obinutuzumab | Humanized, glycoengineered IgG1 | IV | CLL, FL | Higher ADCC than rituximab; IRR common, cytopenias |
| Ofatumumab | Fully human IgG1 | IV | CLL, MS (off-label in oncology limited) | Infusion reactions, less immunogenic than rituximab; cytopenias |
Administration & Dosing Highlights
- IV infusion (most common), sometimes subcutaneous (ofatumumab).
- Premedication recommended: acetaminophen + antihistamine ± corticosteroid.
- Infusion rate: start slow, escalate gradually; reduce or stop if IRR occurs.
Key Toxicities
- Infusion-related reactions (IRR) – fever, chills, hypotension, rash; most occur during first infusion.
- Infections – increased risk due to B-cell depletion; HBV reactivation is a serious risk → screen before therapy.
- Cytopenias – neutropenia, thrombocytopenia.
- Rare: tumor lysis syndrome, cardiac events (rare).
Monitoring
- CBC before each cycle; monitor for neutropenia and infections.
- Hepatitis B screening before therapy.
- Vital signs during infusion.
- Immunoglobulin levels if long-term therapy (risk of hypogammaglobulinemia).
Summary
Anti-CD20 antibodies (rituximab, obinutuzumab, ofatumumab) are cornerstone therapies in B-cell malignancies. They deplete B-cells via ADCC, CDC, and apoptosis. Main concerns are infusion reactions, infection risk (especially HBV reactivation), and cytopenias. Proper premedication and monitoring are essential.