About 25 percent of adults and about 3 percent of children have an ALL subtype called “Ph-positive ALL” (also known as either “Ph+” or “Philadelphia chromosome-positive ALL”). In Ph+ ALL the Philadelphia chromosome contains the abnormal BCR-ABL fusion gene that makes an abnormal protein that helps leukemia cells to grow.
Tyrosine Kinase Inhibitors
Tyrosine kinase inhibitors (TKIs) are used to treat Ph+ ALL by blocking (inhibiting) the BCR-ABL protein from sending signals that cause leukemia cells to form. TKIs are a type of targeted therapy. Targeted therapy uses drugs or other substances that target and attack specific cancer cells but are less likely to harm normal cells.
Tyrosine kinase inhibitors alone are generally not used to treat ALL. Instead, they are added to a combination chemotherapy regimen. These drugs are taken daily as pills. The following TKIs are available to treat Ph+ ALL:
- Imatinib (Gleevec®), taken by mouth, is approved for adult patients with relapsed or refractory Ph+ ALL and pediatric patients with newly diagnosed Ph+ ALL in combination with chemotherapy
- Dasatinib (Sprycel®), taken by mouth, is approved for
- Adults with Ph+ ALL with resistance or intolerance to prior therapy
- Pediatric patients 1 year of age and older with newly diagnosed Ph+ ALL in combination with chemotherapy
- Ponatinib (Iclusig®), taken by mouth, is approved for the treatment of adult patients with T315I-positive Ph+ ALL.
Common side effects of TKIs include low blood counts, abnormal bleeding and pain, nausea and vomiting, diarrhea, fatigue, rashes, headaches and muscle, bone and joint pain. They may also cause fluid to collect under the eyes, and in the hands, feet or lungs. Uncommon, but serious, side effects include a change in the rhythm of the heart, blood vessel narrowing or blood clot formation. Dasatinib may cause fluid to collect around the lungs. Ponatinib side effects may include blood clots, narrowing of blood vessels, heart attack, stroke, liver problems, or inflammation of the pancreas.