Gemtuzumab is a targeted immunotherapy for acute myeloid leukemia (AML), combining:
- Anti-CD33 antibody (binds CD33, a surface marker on AML blasts).
- Calicheamicin (a potent cytotoxic antibiotic payload).
Mechanism of Action
- Targeting: Binds CD33 (expressed in ~90% of AML cases).
- Internalization: Delivers calicheamicin into the cell → causes DNA double-strand breaks → apoptosis.
Key Indications
- Newly diagnosed CD33+ AML (in adults and pediatric patients ≥1 month old).
- Relapsed/refractory CD33+ AML (as monotherapy or with chemotherapy).
Dosing & Administration
- Fractionated dosing (e.g., 3 mg/m² on Days 1, 4, and 7) reduces toxicity.
- Given IV (short infusion).
Efficacy
- Improves event-free survival (EFS) and overall survival (OS) in favorable/intermediate-risk AML (e.g., core-binding factor AML).
- Lower doses (3 mg/m²) are safer and more effective than earlier high-dose regimens.
Side Effects
- Myelosuppression (prolonged cytopenias).
- Liver toxicity (veno-occlusive disease/sinusoidal obstruction syndrome, especially post-transplant).
- Infusion reactions (fever, hypotension).
Key Considerations
- CD33 testing not required (nearly all AML blasts express it, but levels vary).
- Avoid in severe hepatic impairment or post-stem cell transplant (high VOD risk).
Clinical Pearls
- Most beneficial in low/intermediate-risk AML (e.g., *CBF-AML, NPM1-mutated*).
- Not used in APL (due to high CD33 expression but better alternatives like ATRA/ATO).
Key Takeaway
Gemtuzumab ozogamicin is a CD33-directed chemoimmunotherapy for AML, offering survival benefits in select patients but requiring careful monitoring for liver toxicity.
Synonyms
Mylotarg