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

Abstract

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/m2 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.

• Authors: Frédéric Millot, Meinolf Suttorp, Anne B Versluys, Krzysztof Kalwak, Brigitte Nelken, Stephane Ducassou, Yves Bertrand, André Baruchel
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 136 Pg. 107-112 (09 2020) ISSN: 1879-0852 [Electronic] England
• PMID: 32668374 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier Ltd. All rights reserved.

Chemical References

• Imidazoles
• Pyridazines
• ponatinib
• Fusion Proteins, bcr-abl

Topics

• Adolescent
• Age of Onset
• Child
• Child, Preschool
• Female
• Fusion Proteins, bcr-abl (genetics)
• Humans
• Imidazoles (therapeutic use)
• International Cooperation
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy, epidemiology, genetics, pathology)
• Male
• Philadelphia Chromosome
• Pyridazines (therapeutic use)
• Registries
• Retrospective Studies
• Survival Analysis
• Treatment Outcome