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Expert Opin Drug Saf. 2018 Jun;17(6):623-628. doi: 10.1080/14740338.2018.1480719. Epub 2018 May 30.

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

Author information

1
a Hematology, Department of Cellular Biotechnologies and Hematology , Policlinico Umberto 1, 'Sapienza' University , Rome , Italy.
2
b GIMEMA data center.
3
c Hematology Division, IRCCS Ca' Granda - Maggiore Policlinico Hospital Foundation , University of Milan , Milan , Italy.
4
d Hematology , Federico II' University of Naples , Naples , Italy.
5
e Hematology , S. Eugenio Hospital , Rome , Italy.
6
f Hematology, Careggi Hospital , Florence University , Florence , Italy.
7
g Hematology, Azienda Ospedaliero Universitaria Città della Salute e della Scienza , Torino.
8
h Hematology , University of Udine , Udine , Italy.
9
i Institute of Hematology "L. and A. Seràgnoli", University Hospital , University of Bologna , Bologna , Italy.
10
j Dip. Medicina-Università Campus Bio-Medico , Roma.

Abstract

INTRODUCTION:

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.

AREAS COVERED:

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.

EXPERT OPINION:

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 evaluate QoL during treatment with TKIs and how to include ponatinib among possible option for intolerant patients.

KEYWORDS:

Chronic myeloid leukemia; QoL; intolerance; safety; tyrosine kinase inhibitors

PMID:
29845876
DOI:
10.1080/14740338.2018.1480719
[Indexed for MEDLINE]

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