FDA approves dasatinib for children with Philadelphia chromosome-positive chronic myeloid leukemia

The FDA expanded the indication for dasatinib to include the treatment of children with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase.

The approval was granted under priority review and the indication received orphan drug designation.

The agency based the approval of dasatinib (Sprycel, Bristol Myers-Squibb) — a tyrosine kinase inhibitor — on data from two open-label, nonrandomized pediatric studies of 97 patients with Philadelphia chromosome-positive CML.

“While chronic myeloid leukemia is rare in children, accounting for less than 3 percent 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,” Vickie Buenger, PhD, president of Coalition Against Childhood Cancer, said in a press release.

“The FDA’s decision to approve the expanded use of [dasatinib] in children with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase may bring new hope to these patients and their families.”

In a single-arm trial, 51 of 97 patients had newly diagnosed Philadelphia chromosome-positive CML and 29 patients were resistant or tolerant to previous treatment with imatinib. In a dose-ranging trial no patients had newly diagnosed Philadelphia chromosome-positive CML and 17 were resistant or intolerant to imatinib.

Ninety-one of the 97 pediatric patients with Philadelphia chromosome-positive CML received dasatinib (60 mg/m² once daily, maximum dose of 100 mg once daily for patients with high body surface area). Patients received treatment until disease progression or unacceptable toxicity.

The efficacy endpoints included complete cytogenetic response (CCyR), major cytogenetic response (MCyR) and major molecular response (MMR).

With a median follow-up of 4.5 years in newly diagnosed patients, the median durations of CCyR, MCyR and MMR could not be estimated because more than half of the responding patients had not progressed at the time of data cut-off.

Range of duration of response was 2.5 to 66.5 months for CCyR, 1.4 to 66.5 months for MCyR, 5.4 to 72.5 months for subjects who achieved MMR by month 24 and 0.03 to 72.5 months for subjects who achieved MMR at any time.

With a median follow-up of 5.2 years in imatinib-resistant or -intolerant patients, the median durations of CCyR, MCyR and MMR could not be estimated, as more than half the responding patients had not progressed at the time of data cut-off. Range of duration of response was 2.4 to 86.9 months for CCyR, 2.4 to 86.9 months for MCyR and 2.6 to 73.6 months for MMR.

Drug-related serious adverse events were reported in 14.4% of participants. The most common — 15% or more — included myelosuppression, headache, nausea, diarrhea, skin rash, pain in extremity and abdominal pain. Other adverse events can include bleeding-related events, fluid retention, cardiovascular events, pulmonary arterial hypertension and embryo-fetal toxicity. It may also affect the growth and development of pediatric patients.

Options for pediatric patients with CML are limited, and there are few clinical trials investigating potential new treatments in this small patient population, according to Lia Gore, MD, associate professor in the division of medical oncology at University of Colorado School of Medicine and Children’s Hospital Colorado.

“Dasatinib is an important new option to help address the unmet needs of children with Philadelphia chromosome-positive CML in chronic phase,” Gore said.