Introduction
Mylotarg (gemtuzumab ozogamicin) is a targeted immunoconjugate therapy approved for the treatment of CD33-positive acute myeloid leukemia (AML). This monoclonal antibody-drug conjugate represents a significant advancement in the treatment of specific AML populations, combining targeted delivery with potent cytotoxic effects.
Mechanism of Action
Mylotarg is a humanized IgG4 kappa monoclonal antibody conjugated to a cytotoxic calicheamicin derivative. The antibody component binds specifically to CD33 antigens expressed on leukemic blasts and normal myeloid cells. Following binding and internalization, the calicheamicin derivative is released intracellularly and binds to DNA in the minor groove, causing double-strand DNA breaks and subsequent cell death.
Indications
- Newly diagnosed CD33-positive AML in adults
- Relapsed or refractory CD33-positive AML in adults and pediatric patients 2 years and older
- Specifically indicated as monotherapy or in combination with chemotherapy regimens
Dosage and Administration
Adults:- Induction: 3 mg/m² (up to one 4.5 mg vial) on Days 1, 4, and 7 in combination with daunorubicin and cytarabine
- Monotherapy: 6 mg/m² on Day 1 and 3 mg/m² on Day 8 for one cycle
- 3 mg/m² on Days 1, 4, and 7 when combined with chemotherapy
- Intravenous infusion over 2 hours
- Premedication with corticosteroids, antihistamines, and acetaminophen recommended
- Do not administer as IV push or bolus
- Hepatic impairment: Use with caution in patients with bilirubin >2× ULN
- Renal impairment: No dosage adjustment recommended
- Elderly: Monitor closely for increased toxicity
Pharmacokinetics
Absorption: Administered intravenously, achieving complete bioavailability Distribution: Volume of distribution approximately 10-12 L; binds to CD33-positive cells Metabolism: Proteolytic degradation; calicheamicin derivative metabolized via non-enzymatic reduction and hydrolysis Elimination: Biphasic elimination with terminal half-life of 72-96 hours; primarily hepatic clearanceContraindications
- History of severe hypersensitivity to gemtuzumab ozogamicin or any component of the formulation
- Patients with known hypersensitivity to calicheamicin derivatives
Warnings and Precautions
Boxed Warning:- Hepatotoxicity, including hepatic veno-occlusive disease (VOD)
- Increased risk of VOD in patients who undergo hematopoietic stem cell transplant after Mylotarg
- Myelosuppression with increased risk of infection and bleeding
- Infusion-related reactions
- Monitor for signs and symptoms of VOD (weight gain, right upper quadrant pain, hepatomegaly, ascites)
- Increased risk of hemorrhage due to thrombocytopenia
- QT interval prolongation reported
- Embryo-fetal toxicity
Drug Interactions
- Strong CYP3A4 inhibitors: May increase calicheamicin exposure
- Strong CYP3A4 inducers: May decrease calicheamicin exposure
- Other myelosuppressive agents: Additive myelosuppression
- Hepatotoxic drugs: Increased risk of liver toxicity
Adverse Effects
Very Common (≥10%):- Febrile neutropenia (68%)
- Hemorrhage (37%)
- Infection (27%)
- Nausea (27%)
- Vomiting (19%)
- Constipation (25%)
- Headache (19%)
- Elevated liver enzymes (AST/ALT increase)
- Hepatic veno-occlusive disease (12%)
- Severe infusion reactions
- Persistent myelosuppression
- Tumor lysis syndrome
- QT interval prolongation
Monitoring Parameters
Prior to each dose:- Complete blood count with differential
- Liver function tests (AST, ALT, total bilirubin)
- Renal function tests
- Electrolytes including magnesium and potassium
- Monitor for infusion reactions
- Vital signs every 30 minutes
- Weekly CBC until recovery
- Liver function monitoring for at least 30 days
- Signs/symptoms of VOD for several months
- ECG monitoring if risk factors for QT prolongation
Patient Education
- Report any signs of infection (fever, chills) immediately
- Monitor for bleeding or bruising tendencies
- Report right upper quadrant pain, rapid weight gain, or abdominal swelling
- Use effective contraception during treatment and for several months after
- Avoid pregnancy during treatment
- Inform all healthcare providers about Mylotarg treatment
- Report any infusion-related symptoms during administration
References
1. FDA Prescribing Information: Mylotarg (gemtuzumab ozogamicin) 2. Lancet JE, et al. Final efficacy and safety results of gemtuzumab ozogamicin in patients with acute myeloid leukemia. Blood. 2018;132(Supplement 1):464. 3. Petersdorf SH, et al. A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia. Blood. 2013;121(24):4854-4860. 4. Castaigne S, et al. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012;379(9825):1508-1516. 5. NCCN Clinical Practice Guidelines in Oncology: Acute Myeloid Leukemia. Version 2.2023.