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# Mylotarg (gemtuzumab ozogamicin)
## Overview
Mylotarg is a CD33-directed antibody-drug conjugate (ADC). It consists of a monoclonal antibody linked to the cytotoxic agent calicheamicin, which causes DNA double-strand breaks, leading to apoptosis in CD33-positive leukemic cells.
## Primary Indications
* Treatment of newly diagnosed CD33-positive acute myeloid leukemia (AML) in adults and pediatric patients aged 1 month and older.
* Treatment of relapsed or refractory CD33-positive AML in adults and pediatric patients aged 2 years and older.
## Adult Dosing
* **Newly Diagnosed AML (Combination):** 3 mg/m² (max 4.5 mg per single dose) on Days 1, 4, and 7 in combination with daunorubicin and cytarabine.
* **Relapsed/Refractory AML (Monotherapy):** 9 mg/m² as a single dose on Day 1. If evidence of disease persists after the first dose, a second dose of 9 mg/m² may be administered 14 days later.
* *Note: Dosing is highly regimen-specific; consult local clinical protocols.*
## Pediatric Dosing
* **Newly Diagnosed AML:** 3 mg/m² (max 4.5 mg) on Days 1, 4, and 7 in combination with chemotherapy. For patients with a body surface area (BSA) <0.6 m², the dose is 0.1 mg/kg.
* **Relapsed/Refractory AML:** 3 mg/m² (max 4.5 mg) on Days 1, 4, and 7. For patients with BSA <0.6 m², use 0.1 mg/kg.
## Dose Adjustments
* **Hepatic Impairment:** Avoid use in patients with severe hepatic impairment (total bilirubin >2x ULN). Close monitoring required for mild-to-moderate impairment.
* **Toxicity:** Suspend doses for severe infusion-related reactions or evidence of veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS).
## Contraindications
* Known hypersensitivity to gemtuzumab ozogamicin or any of its components.
* Patients with prior severe or life-threatening hypersensitivity to gemtuzumab ozogamicin.
## Adverse Effects
* **Severe/Fatal:** Veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS), particularly in patients undergoing hematopoietic stem cell transplantation (HSCT) post-therapy.
* **Common:** Hemorrhage, hepatotoxicity, infection, neutropenia, thrombocytopenia, nausea, and infusion-related reactions.
* **Other:** QTc interval prolongation.
## Key Drug Interactions
* **Hepatotoxic Agents:** Increased risk of hepatotoxicity when combined with other drugs known to cause liver damage.
* **Strong CYP3A4 inhibitors/inducers:** While not primarily metabolized by CYP450, exercise caution as systemic exposure might be affected by multi-drug regimens.
## Monitoring
* **Liver Function:** Transaminases, alkaline phosphatase, and total bilirubin before each dose.
* **Hematology:** CBC with differential and platelets frequently during therapy.
* **VOD/SOS:** Monitor for sudden weight gain, right upper quadrant pain, ascites, and hepatomegaly, especially if post-Mylotarg HSCT is planned.
* **Infusion:** Monitor for signs of infusion-related reactions (fever, chills, hypotension). Premedication (corticosteroid, antihistamine, antipyretic) is required.
## Clinical Pearls
* **VOD Risk:** The risk of VOD is significantly increased in patients receiving Mylotarg who subsequently undergo HSCT. If possible, avoid hepatotoxic conditioning regimens.
* **Premedication:** Always administer premedication 1 hour prior to infusion to mitigate the risk of infusion reactions.
* **Handling:** This is a hazardous drug. Use appropriate aseptic techniques for reconstitution and administration; protect from light during infusion.
* **Uncertainty:** Dosing protocols vary significantly between cooperative group trials (e.g., COG, SWOG) and institutional standards; always confirm the specific protocol for the intended induction or consolidation phase.
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*Disclaimer: This information is for educational purposes only. Always consult the most current FDA-approved labeling, local institutional guidelines, and clinical trial protocols before prescribing or administering any medication.*
