The U.S. Food and Drug Administration has approved a new use of Gleevec (imatinib) to treat children newly diagnosed with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL).
Gleevec was granted accelerated approval in 2001 to treat patients with blast crisis, accelerated phase or chronic phase Ph+ chronic myeloid leukemia (CML) that have failed interferon-alpha therapy. It has since been approved to treat several conditions, most recently regular approval to treat children newly diagnosed with Ph+ CML (2011) and regular approval to treat adults whose Kit (CD117)-positive gastrointestinal stromal tumors (GIST) have been surgically removed (2012).
ALL is the most common type of pediatric cancer with a peak incidence at 2–5 years of age, and another peak in old age. It affects approximately 2,900 children annually, and progresses quickly if untreated. The overall cure rate in children is about 80%, and about 45%-60% of adults have long-term disease-free survival.
Children with Ph+ ALL have a genetic abnormality that causes proteins called tyrosine kinases to stimulate the bone marrow to make too many immature white blood cells, which multiply continuously causing damage and death by crowding out normal cells in the marrow, and by spreading to other organs.
Although the signs and symptoms of ALL are variable, they geberally include: over-all weakness and fatigue; anemia ; frequent or unexplained fever and infection; weight loss and/or loss of appetite; excessive and unexplained bruising; bone pain and joint pain (caused by the spread of “blast” cells to the surface of the bone or into the joint from the marrow cavity); loss of breath; enlarged lymph nodes,liver and/or spleen; swelling in the lower limbs and/or abdomen; and Petechia, which are tiny red spots or lines in the skin due to low platelet levels
Gleevec, a tyrosine kinase inhibitor, blocks the proteins that promote the development of cancerous cells. It should be used in combination with chemotherapy to treat children with Ph+ ALL.
“We are pleased that the number of cancer medications for children are on the rise,” said Richard Pazdur, M.D., 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.”
According to the FDA, Gleevec’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 five years of treatment. 92 patients with Ph+ ALL were enrolled in the trial and divided into five treatment groups, with each successive group receiving a greater duration of Gleevec treatment in combination with chemotherapy.
Approximately half of the Ph+ ALL patients received Gleevec for the longest duration, and 70% of these patients did not experience relapse or death within four years (event-free survival). Results also showed patient deaths decreased with increasing duration of Gleevec treatment in combination with chemotherapy.
The most common side effects observed in children with Ph+ ALL treated with Gleevec in combination with chemotherapy included decreased levels of infection-fighting blood cells called neutrophils; decreased levels of blood platelets, which assist in blood clotting; liver toxicity; and infection.
For more information about the disease contact the Leukemia & Lymphoma Society, 300 Research Pkwy., Meriden, CT 06450 203 379-0445,