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

David S. Sanford, Hagop Kantarjian, Susan O'Brien, Elias Jabbour, Jorge Cortes, Farhad Ravandi

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)365-373
Number of pages9
JournalExpert Review of Anticancer Therapy
Volume15
Issue number4
DOIs
StatePublished - Apr 1 2015
Externally publishedYes

Keywords

  • acute lymphoblastic leukemia
  • adverse events
  • Philadelphia chromosome
  • ponatinib
  • resistance mutations

ASJC Scopus subject areas

  • Oncology
  • Pharmacology (medical)

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