Mylotarg (gemtuzumab ozogamicin) has been approved for the first-line treatment of children, ages one month or older, who have acute myeloid leukemia (AML) positive for the CD33 protein, the U.S. Food and Drug Administration (FDA) announced.
The therapy already had been approved for adults with newly diagnosed AML, and for adults and children ages two years or older with relapsed or refractory AML.
The new approval extension now makes Mylotarg available to adults and children with CD33-positive AML, regardless of the number of prior therapies they have received, the FDA said in a press release.
Mylotarg was developed by Wyeth Pharmaceuticals, which was acquired by Pfizer in 2009. It belongs to a class of therapies known as antibody-drug conjugates, which are essentially made of an antibody targeting a specific cancer protein attached to a toxic compound that kills cancer cells.
The antibody in Mylotarg is designed to bind the CD33 protein, found in more than 90% of AML cells. Once bound to this protein receptor, Mylotarg releases its toxic payload into the cell, triggering its death without harming healthy cells.
The recent pediatric approval was based on data from the AAML0531 Phase 3 trial (NCT00372593), in which first-line treatment with Mylotarg plus chemotherapy was found to work significantly better than chemo alone at extending the time young AML patients lived without disease recurrence or induction failure.
AAML0531 enrolled 1,063 people with acute myeloid leukemia, ages 1 month to 29 years, who had not received any prior treatment for their cancer. The participants were randomly assigned to receive five cycles of chemotherapy alone or with Mylotarg. Mylotarg was administered once on day six of the first chemotherapy induction treatment, and on day seven of the second chemotherapy intensification treatment.
The trial’s main efficacy goal was to determine if the Mylotarg combo extended event-free survival — the length of time after the treatment ends that the patient remains free of complications. That period was measured from the time treatment started to the failure of induction chemotherapy, relapse, or death by any cause, whichever occurred first.
Another primary goal was overall survival at three years, while secondary goals included the proportion of participants achieving leukemia remission, and the risk of relapse.
The results showed that Mylotarg reduced by 16% the risk of disease relapse, chemotherapy failure or death. Five years after treatment initiation, 48% of those taking Mylotarg were alive and event-free, compared with 40% of those on chemo alone.
Overall survival at three years, and remission rates after chemotherapy completion were similar between the two groups. However, additional analyses demonstrated that Mylotarg reduced the risk of relapse by 23%, and was associated with better disease-free survival and treatment-related mortality.
The most common serious adverse events in Mylotarg-treated patients were infection, low levels of neutrophils — a type of immune cells — fever (febrile neutropenia), decreased appetite, high blood sugar (hyperglycemia), inflammation and pain in the mouth and digestive tract (mucositis), and low oxygen levels (hypoxia). Bleeding, markers of liver damage, diarrhea, nausea, and low blood pressure also were common serious adverse events.