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# Mylotarg (gemtuzumab ozogamicin)
## Overview
Mylotarg is a CD33-directed antibody and DNA-binding agent conjugate used in the treatment of acute myeloid leukemia (AML).
## Primary Indications
* Relapsed or refractory CD33-positive AML in adults.
* Newly diagnosed CD33-positive AML in adults in combination with chemotherapy.
## Adult Dosing
**For relapsed or refractory CD33-positive AML:**
* **Cycle 1:** 3 mg/m\(^2\) as a single dose on Day 1.
* **Cycle 2 (if continued):** 3 mg/m\(^2\) as a single dose on Day 1.
* **Cycle 3 (if continued):** 3 mg/m\(^2\) as a single dose on Day 1.
**For newly diagnosed CD33-positive AML (in combination with chemotherapy):**
* Administer 3 mg/m\(^2\) on Days 4, 7, and 10 of each cycle.
* Alternatively, administer 6 mg/m\(^2\) on Day 4 of each cycle.
**Maximum dose:** There is no defined maximum dose per administration; dosing is based on body surface area.
**Infusion:** Administer intravenously over 2 hours. If a dose interruption or significant infusion reaction occurs, the infusion rate may need to be slowed or stopped.
## Pediatric Dosing
Mylotarg is not approved for use in pediatric patients. Dosing in pediatric patients would typically be determined by investigational protocols and would be highly specific to the protocol's design, often based on BSA. Consult specific pediatric oncology protocols for any established regimens.
## Dose Adjustments
Dose modifications are primarily based on the occurrence and severity of adverse events, particularly veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) and myelosuppression.
* **VOD/SOS:** If VOD/SOS is suspected or confirmed, discontinue Mylotarg permanently.
* **Myelosuppression:** Dose delays or reductions may be necessary based on hematologic recovery and nadir counts. Specific guidance on reduction thresholds and subsequent dosing is protocol-dependent.
## Contraindications
* None listed in standard prescribing information. However, severe hypersensitivity reactions to gemtuzumab ozogamicin or its components are a strong contraindication.
## Adverse Effects
**Serious and potentially fatal adverse reactions include:**
* **Hepatotoxicity, Veno-occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS):** Can occur during treatment, following treatment, and may be dose-dependent. Symptoms include jaundice, hepatomegaly, ascites, and thrombocytopenia.
* **Myelosuppression:** Severe neutropenia, thrombocytopenia, anemia, and febrile neutropenia can occur.
* **Hemorrhage:** Bleeding events, including severe or fatal ones, can occur, particularly in patients with thrombocytopenia.
* **Hypersensitivity Reactions:** Including anaphylaxis.
* **Tumor Lysis Syndrome (TLS):** Especially in patients with a high tumor burden.
* **Embryo-fetal Toxicity:** Due to its mechanism of action.
**Common adverse events:** Nausea, vomiting, diarrhea, stomatitis, fatigue, fever, headache, neutropenia, thrombocytopenia, anemia, elevated liver enzymes.
## Key Drug Interactions
* Generally, no specific drug interactions are highlighted beyond avoiding concomitant administration with other medications that exacerbate myelosuppression or hepatotoxicity.
## Monitoring
* **Liver Function Tests:** Frequently monitor ALT, AST, bilirubin, and alkaline phosphatase, especially for VOD/SOS.
* **Complete Blood Counts (CBC) with differential:** Monitor frequently for myelosuppression.
* **Coagulation Parameters:** Monitor INR, PTT, and platelet counts, especially in patients at risk for bleeding.
* **Renal Function:** Monitor BUN and creatinine.
* **Signs and Symptoms of Hypersensitivity:** Monitor during and after infusion.
* **Signs and Symptoms of TLS:** Monitor electrolytes and clinical signs.
## Clinical Pearls
* Administer Mylotarg as a slow intravenous infusion (over 2 hours) to reduce the risk of infusion-related reactions.
* Premedication with an antihistamine, antipyretic, and corticosteroid may be considered to mitigate infusion reactions.
* VOD/SOS is a critical toxicity; close monitoring of liver function and clinical signs is paramount. Discontinuation is recommended if VOD/SOS is suspected or confirmed.
* Due to the potential for severe myelosuppression, patients should be closely monitored for signs of infection and bleeding.
* Confirm CD33 expression on leukemic cells prior to initiating treatment.
* Counsel patients regarding reproductive potential and the risks of embryofetal toxicity.
