The FDA has extended the approval of gemtuzumab ozogamicin (MylotargTM, Wyeth Pharmaceuticals, LLC) to include pediatric patients aged 1 month and older with newly diagnosed CD33-positive acute myeloid leukemia (AML). Gemtuzumab ozogamicin is a humanized immunoconjugate that targets CD33, a cell surface antigen present in over 80% of patients with AML.
The approval was based on AAML0531 (NCT00372593), a phase 3 trial that enrolled 1,063 patients aged 0 to 29 years with newly diagnosed AML. Patients were randomized to receive standard five-cycle chemotherapy with or without gemtuzumab ozogamicin 3 mg/m2, which was administered once on Day 6 of the first induction course and once on Day 7 of the second intensification course. The trial's primary end point was event-free survival, defined as the time from study entry until induction failure, relapse, or death. Secondary end points included remission rate, relapse risk, disease-free survival, overall survival, and treatment-related mortality.
Gemtuzumab ozogamicin significantly improved event-free survival compared with chemotherapy alone, with a hazard ratio of 0.84. At five years, a higher proportion of patients in the gemtuzumab ozogamicin arm were free of induction failure, relapse, or death compared with those receiving chemotherapy alone (48% vs 40%).
Grade 3/4 adverse events occurring in at least 5% of patients receiving gemtuzumab ozogamicin included infection, febrile neutropenia, decreased appetite, hyperglycemia, mucositis, hypoxia, hemorrhage, increased transaminase, diarrhea, nausea, and hypotension. Fatal adverse events included infection, multi-organ failure, anemia, and hemorrhage.
"Gemtuzumab ozogamicin added to chemotherapy improved event-free survival through a reduction in relapse risk for children and adolescents with AML," concluded the investigators, led by first author Alan S. Gamis, MD, MPH, Associate Division Director of Oncology at the University of Missouri–Kansas City School of Medicine, in their publication of the trial's results in the Journal of Clinical Oncology.
The recommended dose of gemtuzumab ozogamicin is 3 mg/m2 in combination with standard chemotherapy, administered once in the first induction cycle and once in the second intensification cycle.
For More Information
Gamis AS, Alonzo TA, Meshinchi S, et al (2014). Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children's Oncology Group Trial AAML0531. J Clin Oncol, 32(27):3021-32. DOI:10.1200/JCO.2014.55.3628US Food and Drug Administration (2020). FDA approves gemtuzumab ozogamicin for CD33-positive AML in pediatric patients. Available at: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-gemtuzumab-ozogamicin-cd33-positive-aml-pediatric-patients