Ponatinib in childhood Philadelphia chromosome–positive leukaemias: an international registry of childhood chronic myeloid leukaemia study

Background Ponatinib is effective in adults with Philadelphia chromosome–positive (Ph+) leukaemias, but scant data are available regarding the use of this tyrosine kinase inhibitor in children. Aims The aim of this study isto describe the tolerance and efficacy of compassionate use of ponatinib in a paediatric cohort of patients with Ph+ leukaemias. Methods Data from 11 children with chronic myeloid leukaemia (CML) registered to the international registry of childhood chronic myeloid leukaemia and from 3 children with Ph+ acute lymphoblastic leukaemia (Ph+ ALL) treated with ponatinib were collected retrospectively. Results In 11 girls and 3 boys (median age 14 years), ponatinib was used as a second- to eighth-line treatment. Ponatinib was administered as single therapy (9 patients) or in combination with chemotherapy (8 patients). The status of the disease when ponatinib was started was as follows: CML in advanced phases (n = 8), CML in chronic phase without achievement of molecular response (n = 2) or presence of T315I mutation (n = 1) and Ph + ALL in molecular (n = 1) or marrow (n = 2) relapses. The median dose administered was 21.4 mg/m 2 and median duration of ponatinib was 2.5 months. Ponatinib alone or in combination with chemotherapy administered on 16 occasions led to achievement of major molecular response in 50% of cases. Ponatinib was used as a bridge to transplant in 4 cases. Among the 9 patients treated with ponatinib alone, toxicity grade III–IV (2 patients) was exclusively haematologic. No vascular events related to ponatinib were observed. Conclusion Ponatinib may be a reasonable additional treatment option for children with Ph+ leukaemias who have failed several lines of therapy.