Obinutuzumab

• Class: Monoclonal antibody (mAb) – anti-CD20, type II.
• Origin: Humanized, glycoengineered IgG1 antibody.

Mechanism of Action (MOA)

• Binds CD20 on B-cells → induces B-cell depletion.
• Type II anti-CD20 features:
  • Enhanced antibody-dependent cellular cytotoxicity (ADCC) due to glycoengineering.
  • Direct non-apoptotic cell death (lysosomal pathway) stronger than rituximab.
  • Reduced complement-dependent cytotoxicity (CDC) compared to rituximab.

Clinical Uses

• Chronic lymphocytic leukemia (CLL) – in combination with chlorambucil.
• Follicular lymphoma (FL) – first-line or relapsed/refractory:
  • In combination with chemotherapy or as single-agent maintenance.
• Investigational in other B-cell malignancies.

Dosing (Adults)

• CLL (with chlorambucil):
  • Cycle 1: 100 mg IV day 1, then 900 mg IV day 2, 1000 mg IV days 8 & 15.
  • Subsequent cycles: 1000 mg IV day 1 of each cycle.
• FL (with chemotherapy or as single-agent maintenance):
  • 1000 mg IV on days 1, 8, 15 of cycle 1, then day 1 of subsequent cycles.
• Infusion rate: start slow, increase gradually if tolerated.

Toxicities

• Infusion-related reactions (IRRs) – most common, especially first infusion:
  • Fever, chills, hypotension, rash, dyspnea.
  • Premedication: acetaminophen + antihistamine ± corticosteroid.
• Cytopenias: neutropenia, thrombocytopenia, anemia.
• Infections: bacterial, viral (including HBV reactivation).
• Tumor lysis syndrome (TLS) – rare but possible.
• Hepatic toxicity – monitor LFTs.

Monitoring

• CBC (baseline and during therapy).
• Liver function tests.
• Signs of infection.
• Tumor lysis risk for bulky disease – consider hydration/urate-lowering agents.
• Premedication adherence for IRR prevention.

Summary

Obinutuzumab (Gazyva®) is a glycoengineered, type II anti-CD20 mAb used in CLL and follicular lymphoma. Its key concerns are infusion-related reactions, cytopenias, and infection risk, requiring careful premedication and monitoring.