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Ponatinib: A Third-Generation Inhibitor for the Treatment of CML

Chapter
First Online:
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 201)

Abstract

The establishment of imatinib as the standard therapy for CML marked the beginning of a new era of treatment. Due to occurring intolerance and resistance against the drug, developing newer inhibitors was promoted. This led to the second-generation inhibitors dasatinib, nilotinib and bosutinib. Despite all achieved improvement, all first- and second-generation inhibitors are ineffective against the BCR-ABL T315I “gatekeeper” mutation. In order to overcome this issue and to further improve the inhibitory effect, the third-generation inhibitor ponatinib was developed. Various clinical trials have been launched to study the effect of ponatinib in the clinical setting. Based on positive phase 1 and phase 2 trials, ponatinib was approved for the second-line treatment of CML and Ph+ ALL in December 2012 in the United States and in July 2013 in the European Union. Further trials investigate the potential effect of ponatinib in kinase-dependent subgroups of other malignancies. In conclusion, ponatinib has proved to be a powerful BCR-ABL inhibitor, which exhibits clinical activity both in BCR-ABL wild-type and mutant CML, including activity against the T315I mutation. Despite previous TKI failure, chronic-phase CML patients can achieve sustained remissions using the novel drug, offering a new therapeutic option in the treatment for CML.

Keywords

Accelerate Phase Major Molecular Response T315I Mutation Blast Phase Hematologic Adverse Effect 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.University of Freiburg - Medical Center - Department of Medicine IFreiburgGermany

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