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# Mylotarg (gemtuzumab ozogamicin)
## Overview
Mylotarg is an antibody-drug conjugate (ADC) consisting of a humanized anti-CD33 monoclonal antibody conjugated to the cytotoxic agent calicheamicin. It targets CD33-expressing leukemic cells.
## Primary Indications
* Acute Myeloid Leukemia (AML):
* Newly diagnosed AML in adult patients who are 75 years or older and unfit for intensive induction chemotherapy.
* Relapsed or refractory AML in adult patients.
## Adult Dosing
**Newly Diagnosed AML (Patients ≥ 75 years and unfit for intensive induction chemotherapy):**
* **First course:** 3 mg/m² on day 1, 3 mg/m² on day 4, and 3 mg/m² on day 7.
* **Second course (if responders):** 3 mg/m² on day 1, 3 mg/m² on day 4, and 3 mg/m² on day 7.
**Relapsed or Refractory AML:**
* **First cycle:** 6 mg/m² on day 1. May administer a second dose of 3 mg/m² on day 4, provided no unacceptable toxicity occurred with the day 1 dose.
* **Second cycle (if responders):** 3 mg/m² on day 1, 3 mg/m² on day 4, and 3 mg/m² on day 7.
Maximum cumulative dose: 60 mg/m².
## Pediatric Dosing
There is no established pediatric dosing for Mylotarg. Use in pediatric patients is not recommended.
## Dose Adjustments
**Hepatotoxicity:**
* **Hyperbilirubinemia:**
* Total Bilirubin 1.5-3 x ULN: Consider withholding or delaying dose.
* Total Bilirubin > 3 x ULN: Withhold or delay dose.
* Total Bilirubin > 5 x ULN: Discontinue Mylotarg.
* **Veno-occlusive Disease (VOD)/Sinusoidal Obstruction Syndrome (SOS):**
* Grade 1-2 VOD/SOS: Withhold or delay dose.
* Grade 3-4 VOD/SOS: Discontinue Mylotarg.
**Thrombocytopenia:**
* Platelet count < 50,000/mcL: Consider withholding or delaying dose.
**Other Adverse Reactions:**
* Monitor for and manage other toxicities as clinically indicated. Dose interruptions or discontinuations may be necessary based on severity.
## Contraindications
* None listed.
## Adverse Effects
The most common adverse reactions (≥ 20%) include:
* **Hematologic:** Thrombocytopenia, neutropenia, leukopenia, anemia, febrile neutropenia.
* **Gastrointestinal:** Nausea, vomiting, diarrhea, mucositis, abdominal pain, constipation.
* **Infections:** Pneumonia, sepsis, upper respiratory tract infection, urinary tract infection.
* **Hepatobiliary:** Increased AST, increased ALT, increased alkaline phosphatase, hyperbilirubinemia, veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS).
* **Other:** Fever, headache, fatigue, hypokalemia, hypophosphatemia, edema, rash.
**Serious Adverse Reactions:**
* Hepatotoxicity (including VOD/SOS).
* Hemorrhage.
* Myelosuppression.
* Infusion-related reactions.
* Embryo-fetal toxicity.
## Key Drug Interactions
* **Strong CYP3A4 Inhibitors/Inducers:** While not definitively established, caution may be warranted due to the calicheamicin component, although systemic exposure to calicheamicin is low.
* **Other Myelosuppressive Agents:** Concurrent use may exacerbate myelosuppression.
## Monitoring
* **Complete Blood Counts (CBC) with differential:** Frequently monitor for myelosuppression (thrombocytopenia, neutropenia, anemia).
* **Liver Function Tests (LFTs):** Monitor bilirubin and transaminases regularly, especially in patients with pre-existing hepatic impairment.
* **Signs and symptoms of VOD/SOS:** Monitor for fluid retention, jaundice, hepatomegaly, ascites, and thrombocytopenia.
* **Signs and symptoms of bleeding:** Monitor for petechiae, ecchymoses, epistaxis, hematuria, and melena.
* **Signs and symptoms of infusion-related reactions:** Monitor for fever, chills, rash, dyspnea, and hypotension.
* **Pregnancy status:** Assess in women of childbearing potential.
## Clinical Pearls
* Mylotarg is associated with a significant risk of hepatotoxicity, including VOD/SOS, and severe myelosuppression.
* Prophylaxis for VOD/SOS is not routinely recommended but consider based on individual patient risk factors and local protocols.
* Patients should be advised of the risks of embryofetal toxicity and to use effective contraception.
* Due to the risk of severe bleeding, monitor platelet counts closely and manage any bleeding events promptly.
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*This information is intended for healthcare professionals. Always refer to the most current prescribing information and consult with a specialist for patient-specific guidance. Dosing and management may vary based on local protocols and individual patient factors.*
