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# Mylod (Mylotarg / Gemtuzumab ozogamicin) ## Overview Gemtuzumab ozogamicin is a CD33-directed antibody-drug conjugate (ADC). It consists of a monoclonal antibody linked to a cytotoxic agent, calicheamicin, which causes DNA double-strand breaks and subsequent cell death. ## Primary Indications - Treatment of newly diagnosed CD33-positive acute myeloid leukemia (AML) in adults and pediatric patients 1 month and older. - Relapsed or refractory CD33-positive AML in adults and pediatric patients 2 years and older. ## Adult Dosing Dosage is weight-based (actual body weight). Dosing depends on the treatment phase and disease setting. - **Newly Diagnosed AML:** 3 mg/m² (up to a maximum dose of 10 mg equivalent) on days 1, 4, and 7 in combination with daunorubicin and cytarabine. - **Relapsed/Refractory AML:** 3 mg/m² (up to a maximum dose of 10 mg equivalent) on days 1, 4, and 7. - *Note:* Always verify the specific treatment protocol (e.g., induction vs. consolidation) as total doses per cycle vary. ## Pediatric Dosing - **Aged 1 month and older (Newly Diagnosed):** 3 mg/m² (up to 10 mg maximum) on days 1, 4, and 7. - **Aged 2 years and older (Relapsed/Refractory):** 3 mg/m² (up to 10 mg maximum) on days 1, 4, and 7. - *Note:* Dose capping at 10 mg is essential regardless of BSA in patients with high body surface area. ## Dose Adjustments - **Hepatic Impairment:** Avoid use in patients with severe hepatic impairment (total bilirubin > 2x ULN, or AST/ALT > 2.5x ULN). No specific dose adjustments are provided for mild-to-moderate impairment, but extreme caution is required. - **Toxicity:** If severe infusion-related reactions occur, consider dose interruption or discontinuation. ## Contraindications - Known hypersensitivity to gemtuzumab ozogamicin or any component of the formulation. - History of veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS). ## Adverse Effects - **Hepatotoxicity:** Including fatal veno-occlusive disease (VOD)/SOS. - **Myelosuppression:** Grade 3/4 neutropenia, thrombocytopenia, and anemia. - **Infusion-related reactions:** Including hypotension, bronchospasm, and anaphylaxis. - **Infections:** High risk of opportunistic infections due to prolonged cytopenia. - **Hemorrhage:** Often secondary to thrombocytopenia. ## Key Drug Interactions - **Strong CYP3A4 Inhibitors/Inducers:** Use caution, as the calicheamicin payload is metabolized via CYP3A; however, clinical data on significant interaction is limited. - **Hepatotoxic Agents:** Avoid concomitant use with other drugs known to cause liver injury due to increased risk of SOS/VOD. ## Monitoring - **Complete Blood Count (CBC):** Monitor frequently throughout treatment. - **Liver Function Tests (LFTs):** Baseline and prior to each dose; monitor closely for signs of VOD (bilirubin, ALT, AST, alkaline phosphatase). - **Infusion Monitoring:** Observe for at least 1 hour post-infusion for hypersensitivity reactions. - **Coagulation Markers:** Monitor if hemorrhage is suspected. ## Clinical Pearls - **Premedication:** Always administer corticosteroids, antihistamines, and antipyretics 1 hour prior to each dose to reduce infusion reactions. - **VOD Risk:** The risk of VOD is significantly increased in patients undergoing hematopoietic stem cell transplantation (HSCT) following treatment. Monitor LFTs post-HSCT vigilantly. - **Preparation:** Must be reconstituted and diluted strictly according to the manufacturer’s instructions, as the drug is light-sensitive and protein-denaturation prone. - **Pregnancy:** Embryo-fetal toxicity is a known risk; use effective contraception. *** **Educational Disclaimer:** This information is for educational purposes only. Drug dosing, contraindications, and safety protocols change frequently. Always verify the most current prescribing information (package insert) and follow your institution’s specific clinical guidelines before prescribing or administering medication.