Gemtuzumab Ozogamicin in Pediatric Patients With Newly Diagnosed CD33-Positive AML

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On June 16, 2020, the indication of gemtuzumab ozogamicin (Mylotarg) for newly diagnosed CD33-positive acute myeloid leukemia (AML) was extended to include pediatric patients aged 1 month and older.1,2

Supporting Efficacy Data

Approval was supported by findings from the phase III AAML0531 trial ( identifier NCT00372593).2 In the trial, 1,063 patients aged 0 to 29 were randomly assigned to receive five-cycle standard chemotherapy alone (n = 531) or with gemtuzumab ozogamicin at 3 mg/m2 administered once on day 6 in induction cycle 1 and once on day 7 in intensification cycle 2 (n = 532).

The gemtuzumab ozogamicin group included patients in the following age groups: 2 patients < 27 days, 94 patients aged 28 days to 2 years, 225 patients aged 2 years to 12 years, 175 patients aged 12 years to 18 years, and 36 patients ≥ 18 years. Overall, 94% of patients were aged younger than age 18, and 6% were adults; the median age was 9 years; 49% were male; 73% were White, 18% were Hispanic, and 11% were Black; and disease risk status was low in 23% of both groups, intermediate in 57% of both groups, and high in 15% of the gemtuzumab ozogamicin group vs 17% of the chemotherapy group.

The main efficacy outcome measure was event-free survival, measured from the date of trial entry until induction failure, relapse, or death by any cause. The hazard ratio for event-free survival was 0.84 (95% confidence interval [CI] = 0.71–0.99) in favor of the gemtuzumab ozogamicin group; the estimated percentage of patients free of induction failure, relapse, or death at 5 years was 48% (95% CI = 43%–52%) vs 40% (95% CI = 36%–45%). No difference between groups in overall survival was observed.

How It Works

Gemtuzumab ozogamicin is a CD33-directed antibody-drug conjugate (ADC). The antibody portion recognizes human CD33 antigen, and the small molecule portion, N-acetyl gamma calicheamicin, is a cytotoxic agent covalently bound to the antibody via a linker. Preclinical data indicate that gemtuzumab ozogamicin acts via the binding of the ADC to CD33-expressing tumor cells, followed by internalization of the ADC-CD33 complex and intracellular release of N-acetyl gamma calicheamicin dimethyl hydrazide via hydrolytic cleavage of the linker. Activation of N-acetyl gamma calicheamicin dimethyl hydrazide induces double-strand DNA breaks, resulting in cell-cycle arrest and apoptotic cell death.

How It Is Used

The recommended dose of gemtuzumab ozogamicin in pediatric patients aged 1 month and older is 3 mg/m2 for patients with a body surface area (BSA) of at least 0.6 m2 and 0.1 mg/kg for patients with a BSA up to 0.6 m2 via intravenous infusion. For induction cycle 1, the agent is given once in combination with standard chemotherapy; the agent is not given in the second induction cycle. No treatment is given in the first or third intensification cycle. For intensification cycle 2, the agent is given once in combination with standard chemotherapy. The risks and potential benefits of administration should be considered before giving the agent in intensification cycle 2.

Product labeling provides instructions on premedication, including acetaminophen, diphenhydramine, and methylprednisolone and use of methylprednisolone or equivalent for any sign of an infusion reaction during the infusion or within 4 hours afterward. Appropriate measures should be used to prevent tumor-lysis syndrome. Cytoreduction in patients with hyperleukocytosis is recommended prior to administration.

Prescribing information provides instructions on dosage modification, including treatment interruption and discontinuation, for adverse reactions including persistent thrombocytopenia; persistent neutropenia, veno-occlusive disease; hepatic toxicity; infusion-related reactions; and other severe or life-threatening nonhematologic toxicities.

Safety Profile

In the gemtuzumab ozogamicin group in the AAML0531 trial, 520 patients received induction cycle 1 and 326 received intensification cycle 2. The most common grade ≥ 3 adverse events that occurred during induction cycle 1 and intensification cycle 2, respectively, in at least 5% of patients who received gemtuzumab ozogamicin were infection, febrile neutropenia, decreased appetite, hyperglycemia, mucositis, hypoxia, hemorrhage, increased transaminase, diarrhea, nausea, and hypotension.

During intensification cycle 2, prolonged thrombocytopenia (64% vs 55%) and prolonged neutropenia (47% vs 43%) were more common with gemtuzumab ozogamicin, and the prolonged cytopenias were associated with more deaths in remission (5% vs 3%). Veno-occlusive disease events occurred in 5% vs 5% of patients and were fatal in two vs seven patients. Fatal adverse events in the gemtuzumab ozogamicin group consisted of infection in 14 patients, multiorgan failure in 5, hemorrhage in 3, and anemia in 1.

Gemtuzumab ozogamicin has a boxed warning for hepatotoxicity. Hepatotoxicity, including severe or fatal hepatic veno-occlusive disease, also known as sinusoidal obstruction syndrome, has been reported in association with the use of the agent.

Gemtuzumab ozogamicin has warnings/precautions for infusion-related reactions, including anaphylaxis; hemorrhage, including severe and fatal events; and embryofetal toxicity. Patients should be monitored during and for at least 1 hour after the end of infusion. Platelet counts should be monitored frequently. Gemtuzumab ozogamicin is contraindicated in patients with hypersensitivity to the agent or any of its components. Patients should be advised not to breastfeed while receiving gemtuzumab ozogamicin. 


1. U.S. Food and Drug Administration: FDA approves gemtuzumab ozogamicin for CD33-positive AML in pediatric patients. Available at Accessed July 27, 2020.

2. Mylotarg (gemtuzumab ozogamicin) for injection, Wyeth Pharmaceuticals, June 2020. Available at Accessed July 27, 2020.