The FDA approved dasatinib to treat pediatric chronic myeloid leukemia. This drug is the second tyrosine kinase inhibitor, alongside imatinib, approved for this indication and represents an important new option for first- and second-line treatment.

The FDA has approved dasatinib (Sprycel; Bristol-Myers Squibb) to treat children with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in the chronic phase. It is the second tyrosine kinase inhibitor (TKI) approved to treat these patients.

The November 9 decision was based on phase I and II trial data from 97 pediatric patients who were either newly diagnosed with chronic-phase CML or who were resistant to or intolerant of the TKI imatinib. After 24 months of treatment, 96% of newly diagnosed patients and 83% of those resistant to or intolerant of imatinib exhibited a complete cytogenic response. After a median of roughly 5 years of follow-up, more than half of responders had not experienced disease progression.

Adverse reactions were reported in 10% of patients, and the most common side effects were nausea, diarrhea, and skin rash. “The incidence of severe side effects was extremely low,” says Lia Gore, MD, professor of Pediatrics, Medical Oncology, and Hematology at the University of Colorado Anschutz Medical Campus in Aurora and one of the phase II trial researchers. “There were no pleural effusions, pericardial effusions, or pulmonary arterial hypertension events reported, all of which have been seen in adults treated with dasatinib.”

Studying pediatric CML has been notoriously difficult because it accounts for just 3% of newly diagnosed childhood leukemias. To conduct the dasatinib trials, investigators pooled patients from 18 countries across four continents. “One of the things that we are very proud of in this study is the international collaboration,” says Gore.

The result is a major advance for patients. “There are a number of TKIs approved for use in adults with CML, but until now only one for pediatric patients,” says Lewis Silverman, MD, clinical director of the Pediatric Hematologic Malignancies Center at Dana-Farber Cancer Institute in Boston, MA. “To have a second FDA-approved option is really important.”

Kirk Schultz, MD, director of the Michael Cuccione Childhood Cancer Research Program at BC Children's Hospital Research Institute in Vancouver, Canada, says that “dasatinib is a critical second-line drug for patients who do not tolerate or respond well to imatinib.”

The drug may also be used as a first-line treatment. “There are enough data in adults to suggest that starting off with dasatinib may be beneficial in terms of rapidity of response, so I think many clinicians may use this as front-line treatment for children with CML,” says Silverman.

Administering dasatinib to children in its currently approved form, oral tablets, can be difficult, so an oral solution is currently in development. “Having the powdered formulation for oral suspension as an option for very young patients or patients who cannot otherwise swallow pills is a very important advance,” says Gore. Investigators hope for approval “within the next year or two.”

In addition, because the TKIs used to treat CML are typically also active in Ph+ acute lymphoblastic leukemia, “having the drug available and approved for pediatric use could help facilitate further studies of it for that indication as well,” says Silverman. –Kristin Harper