The role of ponatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia

Expert Review of Anticancer Therapy
David S SanfordFarhad Ravandi

Abstract

The introduction of tyrosine kinase inhibitors has improved outcomes in Philadelphia chromosome-positive acute lymphoblastic leukemia, yet relapse due to the development of resistance mutations remains a major obstacle. Ponatinib is a novel tyrosine kinase inhibitor designed to overcome single-resistance mutations in the ABL kinase. Three clinical trials confirmed the efficacy of ponatinib in the relapsed and front-line setting in Philadelphia positive acute lymphoblastic leukemia, even in the presence of the T315I mutation, which confers resistance to other tyrosine kinase inhibitors. The rate of relapse appears to be very low when used in combination with chemotherapy, suggesting a role for ponatinib in newly diagnosed patients. A major concern with the use of ponatinib is the associated high risk of life-threatening vascular thrombotic events. Potential strategies to reduce this risk include minimizing the use of ponatinib in patients with significant baseline cardiovascular risk, careful surveillance and treatment of cardiovascular risk-factors and dose reduction of ponatinib.

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Citations

Jan 17, 2016·British Journal of Haematology·Kirsten Bleckmann, Martin Schrappe
Aug 26, 2017·Current Opinion in Oncology·Maria Ilaria Del PrincipeAdriano Venditti
Aug 7, 2017·Clinical Case Reports·Jasmine NoetzliOlivier Spertini
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Aug 24, 2021·Lancet·Jorge CortesSusanne Saußele

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