PF417 PONATINIB IN CHILDHOOD PHILADELPHIA POSITIVE LEUKEMIAS: THE EXPERIENCE OF THE INTERNATIONAL REGISTRY OF CHILDHOOD CHRONIC MYLELOID LEUKEMIA (I‐CML‐PED‐STUDY)

Abstract

Background:Ponatinib is effective in adults with Philadelphia positive (Ph+) leukemias but only few case reports are available regarding the use of this so far not‐licensed drug in children and adolescents.Aims:To describe the profile of tolerance and efficacy of compassionate use of ponatinib in children and adolescents with Ph+ leukemias.Methods:Data from 11 children with chronic myeloid leukemia (CML) registered to the I‐CML‐Ped‐Study and from 3 children with Ph+ acute lymphoblastic leukemia (Ph+ ALL) treated with ponatinib were retrospectively collected.Results:In 11 girls and 3 boys (median age 14 years, range: 4.5–17) ponatinib was used as a second (n = 2), third (n = 5), fourth (n = 2), fifth (n = 3), sixth (n = 1) or eighth (n = 1) treatment line. Ponatinib was administered as single therapy in 7 patients while the 7 remaining patients (advanced phases CML n = 5, Ph+ ALL n = 2) received additional chemotherapy. The status of the disease when ponatinib was started was: CML advanced phases (accelerated phase, n = 2; blast crisis, n = 6), CML without achievement of major molecular response (MMR, n = 2), T315I mutation (n = 1) and in Ph+ ALL patients molecular relapse (n = 2) or marrow relapse (n = 1). Six patients were previously transplanted. Ponatinib was used as a bridge to transplant in 5 cases. Dose administered ranged between 15–41 mg/m2 (median: 27 mg/m2) and median duration of ponatinib treatment was 2.5 months (range: 0.5–14 months). Treatment responses in the 8 patients in CML‐advanced phases were: no response (n = 2), complete hematologic response (n = 1), MMR (n = 3), MR4.5 (n = 1) or unknown (n = 1). In patients in CML chronic phase, achievement of MMR was obtained in 2 of the patients without prior achievement of MMR while no response was observed in the patient with mutation T315I. Two of the 3 patients with Ph+ ALL achieved MR4.5 and MR5 while the remaining patient did not respond. Grade 1 to 4 side effects were recorded in 5 of 7 patients treated with ponatinib alone; toxicity grade 3–4 was reported in 2 patients (hematologic toxicity). No vascular event related to ponatinib was observed.Summary/Conclusion:With the limitation of the retrospective nature of this study, ponatinib may be a reasonable additional treatment option for children with Ph+ leukemias who failed to several lines of therapy.