The FDA approved a new use of imatinib (Gleevec) to treat children newly diagnosed with Philadelphia chromosome–positive acute lymphoblastic leukemia (ALL).
ALL is the most common type of pediatric cancer, affecting approximately 2,900 children annually, and progresses quickly if untreated. Children with Philadelphia chromosome–positive ALL have a genetic abnormality that causes tyrosine kinases to stimulate the bone marrow to make too many immature white blood cells, leaving less room for healthy white blood cells needed to fight infection. Imatinib, a tyrosine kinase inhibitor, should be used in combination with chemotherapy to treat children with Philadelphia chromosome–positive ALL.
“We are pleased that the number of cancer medications for children are on the rise,” said Richard
Pazdur, MD, Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Today’s approval is the result of continuous interactions among the FDA, the Children’s Oncology Group, and the National Cancer Institute to provide new and better treatments to American children with cancer.”
Safety Data
Imatinib’s safety and effectiveness for this new indication were established in a clinical trial conducted by the Children’s Oncology Group, sponsored by the National Cancer Institute. The trial enrolled children and young adults 1 year and older with very high risk ALL, defined as patients with a greater than 45% chance of experiencing complications from their disease within 5 years of treatment. Ninety-two patients with Philadelphia chromosome–positive ALL were enrolled in the trial and divided into five treatment groups, with each successive group receiving a greater duration of imatinib treatment in combination with chemotherapy.
Fifty of the patients with Philadelphia chromosome–positive ALL received imatinib for the longest duration, and 70% of these patients achieved event-free survival within 4 years. Results also showed patient deaths decreased with increasing duration of imatinib treatment in combination with chemotherapy.
The most common side effects observed in children with Philadelphia chromosome–positive ALL treated with imatinib in combination with chemotherapy included decreased levels of neutrophils, decreased levels of blood platelets, liver toxicity, and infection.
Imatinib was granted accelerated approval in 2001 to treat patients with blast-crisis, accelerated-phase, or chronic-phase Philadelphia chromosome–positive chronic myeloid leukemia (CML) who have failed interferon-alpha therapy. It has since been approved to treat several conditions, and most recently received regular approval to treat children with newly diagnosed Philadelphia chromosome–positive CML (2011) and regular approval to treat adults whose Kit (CD117)-positive gastrointestinal stromal tumors have been surgically removed (2012). ■
