The FDA expanded the approval of gemtuzumab ozogamicin to include an indication for the treatment of newly diagnosed pediatric patients with CD33-positive acute myeloid leukemia, which includes patients as young as 1 month old.
The FDA expanded the approval of gemtuzumab ozogamicin (Mylotarg) to include an indication for the treatment of newly diagnosed pediatric patients with CD33-positive acute myeloid leukemia (AML), which includes patients as young as 1 month old.
This approval is based on findings from the phase 3 AAML0531 study (NCT00372593). For this study, 1063 patients with newly diagnosed AML between the ages of 0 and 29 years of age were randomized to receive gemtuzumab ozogamicin at a 3 mg/m2 dose once on day 6 in the induction 1 phase and once on day 7 in the intensification 2 phase with or without 5-cycle chemotherapy.
The primary end point of the study was event-free survival (EFS), which was measured from the date of trial entry to induction failure, relapse, or death due to any cause. Investigators found a hazard ratio for EFS of 0.84 (95% CI, 0.71-0.99), and an estimated 48% of patients were free of induction failure, relapse, or death at 5 years (95% CI, 43-52) in the combination arm versus 40% in the chemotherapy alone arm (95% CI, 36-45). There were no differences in overall survival between the 2 arms.
For the gemtuzumab ozogamicin regimen with chemotherapy, the most common grade 3 or greater adverse events (AEs) occurring in at least 5% of patients included infection, febrile neutropenia, decrease appetite, hyperglycemia, mucositis, hypoxia, hemorrhage, increased transaminase, diarrhea, nausea, and hypotension.
The primary objective of this multicenter study was to assess the combination regimen in comparison with chemotherapy alone for younger patients with newly diagnosed AML. The study was conducted because whether chemotherapy was more effective in combination with the agent was unknown, despite understanding that the combination of these 2 treatments could kill more tumor cells.
Another co-primary end point for this study was overall survival at 3 years, while secondary end points included remission induction rate after 2 courses of induction therapy, disease-free survival, mortality, time to marrow recovery, and toxicities.
To be included in the AAML0531 study, patients had to have newly diagnosed AML, meeting the customary criteria with ≥20% bone marrow blasts, and be at least 1 month of age. Those with down syndrome ≥4 years were eligible to enroll, but patients with juvenile myelomonocytic leukemia, Fanconi’s anemia, Kostmann syndrome, Schwachman syndrome, other bone marrow failure syndromes, promyelocytic leukemia or a secondary or treatment-related AML were ineligible for the study. Patients who had received prior chemotherapy, radiation therapy, an anti-leukemic therapy, or any other prior treatment for AML were unable to enroll, and patients with a matched family donor also could not have concurrent peripheral blood stem cell transplant.
This agent was previously approved for the treatment of adult patients with newly diagnosed AML who are determined to be CD33-positive. Gemtuzumab ozogamicin is also approved in the European Union for this patient population.
FDA approves gemtuzumab ozogamicin for CD33-positive AML in pediatric patients. News Release. FDA. June 16, 2020. Accessed June 16, 2020. https://bit.ly/37xYqh8