- Class: Monoclonal antibody – anti-CD20, type I.
- Origin: Fully human IgG1 mAb.
Mechanism of Action (MOA)
- Binds CD20 on B-cells at a different epitope than rituximab (more membrane-proximal).
- Induces B-cell depletion via:
- Complement-dependent cytotoxicity (CDC) – very potent.
- Antibody-dependent cellular cytotoxicity (ADCC) – moderate.
- Less direct apoptosis induction than type II anti-CD20 antibodies (e.g., obinutuzumab).
Clinical Uses
- Chronic lymphocytic leukemia (CLL) – relapsed/refractory or previously untreated (with/without chemo).
- Other hematologic malignancies – investigated off-label (non-Hodgkin lymphoma).
- MS indication (Kesimpta®) is separate (autoimmune, not oncology).
Dosing (Oncology)
- IV infusion:
- Cycle 1: 300 mg day 1, 1,000 mg day 8, 1,000 mg day 15.
- Subsequent cycles: 1,000 mg IV day 1 of each cycle (every 28 days, per protocol).
- Premedication recommended: acetaminophen + antihistamine ± corticosteroid.
- Infusion rate: start slow; increase gradually if tolerated.
Toxicities
- Infusion-related reactions (IRRs) – most common during first infusion: fever, chills, hypotension, rash, dyspnea.
- Cytopenias: neutropenia, thrombocytopenia, anemia.
- Infections: bacterial, viral (HBV reactivation).
- Tumor lysis syndrome – rare but possible.
- Hepatic toxicity – monitor LFTs.
Monitoring
- CBC with differential.
- Liver function tests.
- Signs of infection.
- Tumor lysis risk if high tumor burden.
- Premedication adherence for IRR prevention.
Summary
Ofatumumab (Arzerra®) is a fully human type I anti-CD20 mAb used mainly in CLL. Its primary risks are infusion reactions, cytopenias, and infection, and careful monitoring plus premedication is critical.