Dasatinib CA180226

Summary

Dasatinib is safe and effective in children with CML

Until recently, imatinib was the only tyrosine kinase inhibitor (TKI) targeting BCR-ABL1 that was approved for children with chronic myeloid leukemia (CML). However, about 30% of children had to stop imatinib due to resistance or side effects.

In an international phase 2 study, 84 children with newly diagnosed CML and 29 children with CML who were resistant or intolerant to imatinib were treated with dasatinib. The results show that dasatinib works rapidly and leads to a deep response in many children.

Oral suspension

Dasatinib is given once daily and can be taken with food. For children who have difficulty swallowing tablets, an oral suspension has been developed. Because the suspension is absorbed slightly less efficiently by the body, the dose is slightly higher, 72 mg/m² instead of 60 mg/m². The effectiveness of the suspension was comparable to that of the tablets.

Well tolerated

The deep responses observed with dasatinib make it of interest to further investigate whether it may be possible in the future to stop TKI treatment in some children. At present, there is limited evidence to support this approach.

In addition, dasatinib appears to be well tolerated in children who could not use imatinib due to side effects. Notably, children seem to tolerate dasatinib better than adults. No pleural or pericardial effusions (fluid accumulation around the lungs or the heart) were observed.

The effects of dasatinib on growth and development still need to be studied further with longer follow-up, as growth delay is a known potential side effect of TKIs.

Approval

Based on this phase 2 study and an earlier phase 1 study (Zwaan et al., JCO 2013) both the US and European regulatory authorities have approved dasatinib for use in children with CML.

Would you like to read the scientific publication? Please look here: Gore L, et al. Dasatinib in Pediatric Patients With Chronic Myeloid Leukemia in Chronic Phase: Results From a Phase II Trial. J Clin Oncol. 2018 May 1;36(13):1330-1338.