gemtuzumab ozogamicin — Drug Monograph

Brand names: Mylotarg

Drug class: Antibody-Drug Conjugate

Mechanism of Action

Anti-CD33 humanized monoclonal antibody conjugated to calicheamicin, a highly potent enediyne antibiotic, via an acid-labile hydrazone linker. CD33 is expressed on AML blasts and normal myeloid cells. After receptor-mediated internalization and lysosomal acidification, calicheamicin is released, binds to the minor groove of DNA, and causes double-strand DNA breaks leading to apoptosis.

FDA Indications

• CD33-positive acute myeloid leukemia (AML) in adults: newly diagnosed CD33-positive AML in combination with daunorubicin and cytarabine (favorable-risk cytogenetics benefit)
• Relapsed or refractory CD33-positive AML in adults as monotherapy or in combination
• Relapsed or refractory CD33-positive AML in pediatric patients ≥1 month as monotherapy (approved August 2017 at fractionated dosing)

Common Side Effects

• Myelosuppression (neutropenia, thrombocytopenia, anemia)
• Nausea and vomiting
• Mucositis / stomatitis
• Fatigue
• Fever
• Infusion-related reactions
• ALT/AST elevation

Clinical Pearl

Gemtuzumab ozogamicin has had a turbulent regulatory history — withdrawn in 2010 due to excess early mortality in the SWOG S0106 trial (higher single dose), then re-approved in 2017 after retrospective meta-analysis showed OS benefit at the lower fractionated dosing schedule in favorable-risk cytogenetics. The key clinical lesson: VOD/SOS risk mandates at least a 2-month washout before alloHSCT, and some transplant programs avoid it altogether in patients who are HSCT candidates.

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