Intolerance to tyrosine kinase inhibitors in chronic myeloid leukemia: the possible role of ponatinib

Expert Opinion on Drug Safety
Massimo BrecciaGiorgio Minotti

Abstract

In spite of the proven efficacy of the tyrosine kinase inhibitor (TKI), imatinib, in chronic myeloid leukemia (CML), many patients develop intolerance and discontinue therapy in the long-term. Second-generation TKIs (dasatinib, nilotinib, bosutinib) and the third-generation TKI, ponatinib, have added opportunities but also complexity in the settings of CML treatment. Different definitions of intolerance have been used through several clinical trials, making the published data non homogenous. In most cases, only the severity of acute adverse events (AEs), graded by conventional scales such as Common Terminology Criteria for Adverse Events, was reported. Limited attention to long-term events or more in general, to the impact of AEs on patient quality of life (QoL), remains a problem. Ponatinib is active against all BCR-ABL1 mutants, including T315I, and is widely used to treat patients who developed resistance to other TKIs in any CML phase; however, only limited data is available on the possible role of ponatinib for intolerant patients. We review the different definitions of intolerance used in sponsored trials and in clinical practice, and we discuss how such definitions impact on the management of AEs. We summarize how to eva...Continue Reading

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Citations

Mar 8, 2020·European Journal of Haematology·Luigia LucianoGiorgina Specchia
Jan 5, 2020·Daru : Journal of Faculty of Pharmacy, Tehran University of Medical Sciences·Deepam Pushpam, Sameer Bakhshi
Jun 20, 2020·American Journal of Hematology·Alessandra IurloMassimo Breccia
Mar 12, 2019·Therapeutic Advances in Hematology·Matteo MolicaMassimo Breccia
Jul 24, 2021·International Journal of Clinical Oncology·Yihebali ChiJinwan Wang

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