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# Mylotarg (gemtuzumab ozogamicin)
## Overview
Gemtuzumab ozogamicin is a CD33-directed antibody-drug conjugate (ADC). The anti-CD33 antibody is covalently linked to the cytotoxic agent calicheamicin, which causes DNA double-strand breaks leading to cell cycle arrest and apoptosis.
## Primary Indications
* Newly diagnosed CD33-positive acute myeloid leukemia (AML) in adults and pediatric patients aged 1 month and older.
* Relapsed or refractory CD33-positive AML in adults and pediatric patients aged 2 years and older.
## Adult Dosing
* **Newly Diagnosed AML:** 3 mg/m² (up to a maximum dose of one 4.5 mg vial) on days 1, 4, and 7 in combination with daunorubicin and cytarabine.
* **Relapsed/Refractory AML:** 3 mg/m² on days 1, 4, and 7 as a single agent.
* *Note:* Total dose per course should not exceed 5 mg/m² due to increased risk of hepatotoxicity.
## Pediatric Dosing
* **Weight ≥ 12 kg:** Dosage is based on body surface area (BSA) at 3 mg/m².
* **Weight < 12 kg:** Dosage is based on body weight at 0.1 mg/kg.
* Administration schedules follow the same regimen as adults (days 1, 4, and 7).
## Dose Adjustments
* **Hepatic Impairment:** Avoid use in patients with severe hepatic impairment. Dose reductions are often required for baseline elevated bilirubin (consult institutional protocol).
* **Toxicity:** Delay subsequent doses if severe hematologic or non-hematologic toxicities (specifically hepatotoxicity) occur until resolution or clinical improvement.
## Contraindications
* Known hypersensitivity to gemtuzumab ozogamicin or any of its components.
* History of veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS).
## Adverse Effects
* **Hepatotoxicity:** Including VOD/SOS, elevated LFTs, and hyperbilirubinemia.
* **Infusion-Related Reactions:** Fever, chills, hypotension, and dyspnea (frequently occurs during or shortly after infusion).
* **Myelosuppression:** Profound neutropenia, thrombocytopenia, and anemia.
* **Infections:** Increased risk due to prolonged myelosuppression.
* **Tumor Lysis Syndrome (TLS):** Particularly in patients with high white blood cell counts.
## Key Drug Interactions
* **Hepatotoxic Agents:** Risk of additive hepatotoxicity; use with caution.
* **Live Vaccines:** Avoid live vaccines during treatment due to immunosuppression.
* **QT-Prolonging Agents:** Potential additive effects; monitor ECG in high-risk patients.
## Monitoring
* **Hepatic function:** ALT, AST, total bilirubin, and alkaline phosphatase at baseline and prior to each dose. Monitor closely long-term for VOD/SOS (jaundice, weight gain, ascites, hepatomegaly).
* **CBC:** Monitor blood counts frequently throughout therapy.
* **Infusion:** Monitor for signs of hypersensitivity; premedication (corticosteroids, antihistamines, antipyretics) is mandatory 1 hour prior to infusion.
* **Electrolytes:** Monitor for TLS, especially in patients with high baseline tumor burden.
## Clinical Pearls
* **Preparation:** Must be reconstituted and diluted using aseptic technique; protect from light throughout storage and administration.
* **VOD Risk:** The risk of VOD is significantly increased in patients receiving pre- or post-treatment hematopoietic stem cell transplantation (HSCT).
* **Dosing Limits:** Adherence to the 3 mg/m² limit is critical to reduce the mortality associated with hepatotoxicity.
* **Administration:** Infuse over 2 hours. If a reaction occurs, interrupt the infusion and consider resumption at a slower rate once symptoms resolve.
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*Disclaimer: This information is for educational purposes only. Clinical guidelines and prescribing information change frequently. Always verify current prescribing information, institutional protocols, and FDA-approved labeling before administering any medication.*
