The FDA has expanded the indication for dasatinib tablets (Sprycel, Bristol-Myers Squibb Company) to include the treatment of children with Philadelphia chromosome-positive chronic myeloid leukemia (CML) in chronic phase.
Approval was based on data from 97 pediatric patients with chronic phase CML evaluated in two trials—a phase 1, open-label, nonrandomized, dose-ranging trial and a phase 2, open-label, nonrandomized trial. Fifty-one patients exclusively from the phase 2 trial were newly diagnosed with chronic phase CML and 46 patients (17 from the phase 1 trial and 29 from the phase 2 trial) were resistant or intolerant to previous treatment with imatinib. The majority of patients were treated with dasatinib tablets 60 mg/m2 once daily. Patients were treated until disease progression or unacceptable toxicity.
After 24 months of treatment, 96.1% of newly diagnosed patients (95% confidence interval [CI], 86.5–99.5) and 82.6% of patients resistant or intolerant to imatinib (95% CI, 68.6–92.2) had complete cytogenic response (CCyR). With a median follow-up of 4.5 years in newly diagnosed patients and 5.2 years in imatinib-resistant or -intolerant patients, the median durations of CCyR, major cytogenic response (MCyR), and major molecular response (MMR) could not be estimated as more than half of the responding patients had not progressed at the time of data cut-off.
Adverse reactions reported in more than 10% of dasatinib-treated pediatric patients (n = 97) were headache, nausea, diarrhea, skin rash, vomiting, pain in extremity, abdominal pain, fatigue, and arthralgia. Dasatinib is associated with these warnings and precautions: myelosuppression, bleeding-related events, fluid retention, cardiovascular events, pulmonary arterial hypertension, QT prolongation, severe dermatologic reactions, tumor lysis syndrome, embryo-fetal toxicity and effects on growth and development in pediatric patients.
“While chronic myeloid leukemia is rare in children, accounting for less than 3% of all pediatric leukemias, it is often more aggressive in younger patients than in adults and until recently, there have been few available treatment options,” said Vickie Buenger, President of the Coalition Against Childhood Cancer.
The recommended starting dosage for dasatinib in pediatric patients with Philadelphia chromosome-positive (Ph+) CML in chronic phase is based on body weight. The recommended dose should be administered orally once daily, and the dose should be recalculated every three months based on changes in body weight, or more often if necessary.
In October 2010, dasatinib received accelerated FDA approval for the treatment of adults with newly diagnosed Ph+ CML in chronic phase. The latest approval for dasatinib was granted under priority review, and the indication received orphan drug designation from the FDA.