Mylotarg

Acute myeloid leukemia (AML) — newly diagnosed CD33-positive AML in adults (in combination with daunorubicin and cytarabine); relapsed or refractory CD33-positive AML in adults and pediatric patients ≥1 month old

Newly diagnosed (with chemo): 3 mg/m² (max 4.5 mg) IV Day 1 of induction (up to 2 induction cycles) and Day 1 of 2 consolidation cycles
Relapsed/refractory (single agent): 3 mg/m² IV on Days 1, 4, 7
Infuse over 2 hours through a 0.2 micron in-line filter
Pre-medication: Acetaminophen 650 mg PO, diphenhydramine 50 mg PO or IV, methylprednisolone 1 mg/kg IV 1 hour before each dose
Post-infusion observation: 1 hour for vital signs

For injection: 4.5 mg lyophilized powder in single-dose vial

None listed.

• Hepatotoxicity/VOD/SOS: 3-5% including fatal cases. Higher risk with HSCT. Monitor LFTs frequently. Discontinue for VOD/SOS.
• Infusion-Related Reactions: Including anaphylaxis. Pre-medicate. Monitor for 1 hour after infusion.
• Hemorrhage: Severe and fatal hemorrhage including cerebral hemorrhage, associated with thrombocytopenia.
• QT Prolongation: Monitor ECGs and electrolytes prior to starting and periodically.
• Embryo-Fetal Toxicity

Hemorrhage (99%), infection (84%), nausea (78%), fever (78%), thrombocytopenia (87%), anemia (52%), stomatitis (45%), constipation (42%), vomiting (40%), headache (35%), diarrhea (32%), rash (31%), elevated transaminases (24%), mucositis (18%)

Hepatic VOD/SOS in 5% (incidence higher if given before or after HSCT, may be fatal). Grade 3+ hepatotoxicity in 17%. Infusion-related reactions in 2%. Myelosuppression: Grade 3+ thrombocytopenia (99%), neutropenia (97%), anemia (26%).

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

Hepatic VOD/SOS in 5% (incidence higher if given before or after HSCT, may be fatal). Grade 3+ hepatotoxicity in 17%. Infusion-related reactions in 2%. Myelosuppression: Grade 3+ thrombocytopenia (99%), neutropenia (97%), anemia (26%).

Consult the complete prescribing information for drug interactions, including effects on CYP enzymes, transporters, and concomitant medications that may require dose adjustments or monitoring.

Consult the full prescribing information for pregnancy-related considerations.

Refer to prescribing information for lactation guidance.

Pediatric safety and efficacy information is detailed in the full label.

Dose modifications for organ impairment are specified in the complete prescribing information.

Gemtuzumab ozogamicin is an antibody-drug conjugate comprising a humanized anti-CD33 IgG4 antibody linked to N-acetyl-gamma-calicheamicin dimethylhydrazide (calicheamicin) via an acid-labile linker. CD33 is expressed on the surface of leukemic blasts in >80% of AML patients. Upon binding CD33, the ADC is internalized, and calicheamicin is released in lysosomes, where it binds to DNA minor groove, causing double-strand breaks and apoptosis.

Half-life: approximately 62-90 hours (unconjugated calicheamicin). Clearance decreases after first dose as CD33+ cells are depleted. Tmax: end of infusion. Payload (N-acetyl-gamma-calicheamicin) released after internalization and lysosomal processing.

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

• ALFA-0701 — Gemtuzumab ozogamicin + chemo vs. chemo in newly diagnosed CD33+ AML. Phase III, n=271.
  🔬 NCT00927498 ↗ 📄 Primary Publication ↗

Mylotarg has FDA-approved indications across the following cancer types covered on PipelineEvidence: