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Causes of resistance and treatment choices of second- and third-line treatment in chronic myelogenous leukemia patients

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Abstract

For patients with chronic myelogenous leukemia who fail first-line therapy, several factors should be considered for the decision of the next treatment option. Second-generation tyrosine kinase inhibitors (TKIs) dasatinib, nilotinib, and bosutinib offer improved potency and a high likelihood of success for these patients. Overall, efficacy data are comparable for these agents, and so physicians should consider the BCR-ABL1 mutation profile and the patient’s history to make a decision on the best choice. Only a few BCR-ABL1 mutations seem to be less responsive to any of the three drugs, and it is recommended to choose the second-line TKI that has shown clinical activity against the specific mutation in these cases. For patients with all other mutations and for patients with no mutations, it is recommended to choose the second-generation TKI based on the patient’s disease history. The third-generation TKI ponatinib is available after dasatinib or nilotinib failure or for patients with T315I mutations. However, optimal dose of ponatinib is still under investigation. Overall, it is recommended to select a drug that minimizes the likelihood of worsening the patient’s past side effects or comorbid conditions. In any case, chance and risk of allogeneic stem cell transplantation should be compared with the long-term outcome of TKI therapy in patients eligible for this procedure.

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Conflict of interest

AH received research support from Novartis, BMS, Ariad, Pfizer and MSD.

All other authors do not declare any conflict of interest.

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  1. Abteilung Hämatologie/Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Erlanger Allee 101, 07740, Jena, Germany

    Andreas Hochhaus, Thomas Ernst, Ekkehard Eigendorff & Paul La Rosée

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  1. Andreas Hochhaus
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Correspondence to Andreas Hochhaus.

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Hochhaus, A., Ernst, T., Eigendorff, E. et al. Causes of resistance and treatment choices of second- and third-line treatment in chronic myelogenous leukemia patients. Ann Hematol 94 (Suppl 2), 133–140 (2015). https://doi.org/10.1007/s00277-015-2323-1

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