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Editorial Chronic Myeloid Leukaemia The Management of Chronic Myeloid Leukaemia (CML) Patients with Refractory Disease – Focusing on the Opinions of CML-treating Physicians Ahmet Emre Eskazan Division of Hematology, Department of Internal Medicine, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey A lthough the management of patients with chronic myeloid leukaemia in chronic phase (CML-CP), especially in the newly- diagnosed patient, is generally straightforward, it may vary in the salvage setting, since some of the currently approved tyrosine kinase inhibitors are not available in some countries. This commentary mainly focuses on a questionnaire and the subsequent paper, which were performed in order to understand the perspectives of the CML-treating physicians from different countries in the management of refractory CML-CP. Keywords Chronic myeloid leukaemia, bosutinib, dasatinib, imatinib, nilotinib, ponatinib, refractory, tyrosine kinase inhibitor Disclosure: Ahmet Emre Eskazan has received honoraria from Novartis and Bristol-Myers Squibb. No funding has been received for the publication of this article. This article is a short opinion piece and has not been submitted to external peer reviewers but was reviewed by the editorial board for accuracy before publication. Authorship: All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published. Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit. Received: 3 April 2017 Imatinib (Gleevec ® , Novartis Pharmaceutical Corporation, New Jersey, US) is a BCR-ABL1 tyrosine kinase inhibitor (TKI) that has dramatically improved the outcome of patients with chronic myeloid leukaemia in chronic phase (CML-CP). 1 Although most of the patients with CML-CP do well under imatinib, approximately 40% of them stop receiving imatinib due to lack of efficacy and/or because of intolerance. In the imatinib arm of the International Randomized Study of Interferon and STI571 (IRIS) trial, 34% of patients were no longer on the study drug at 6 years, for reasons that included lack of efficacy (12%) and the occurrence of adverse events (AEs) (4%). 2 Nearly 20% of the patients develop resistance (both primary and acquired), 3 and BCR-ABL1 kinase domain (KD) mutations are detected in approximately 50% of patients with treatment failure and progression. 4 There are various treatment options available for CML patients who remain refractory to the prior line(s) of TKI treatment. 5,6 In patients who fail upfront imatinib therapy, second generation TKIs (2GTKIs; dasatinib, nilotinib and bosutinib) can be administered. 7–9 In addition to 2GTKIs, ponatinib (Iclusig ® ; Ariad Pharmaceuticals, Massachusetts, US) is a potent TKI active against native and mutated forms of BCR-ABL1, including T315I, and it was approved after the phase II PACE study demonstrating that ponatinib was highly active in heavily pretreated Philadelphia chromosome-positive leukaemia patients. 10 Published Online: 1 June 2017 Citation: European Oncology and Haematology, 2017;13(1):15–6 Corresponding Author: Ahmet Emre Eskazan, Istanbul University, Cerrahpasa Faculty of Medicine, Department of Internal Medicine, Division of Hematology, Fatih, Istanbul, Turkey. E: emreeskazan@hotmail.com Although having some differences between each other, in the recommendations of European LeukemiaNet (ELN), 4 the guidelines of National Comprehensive Cancer Network (NCCN) and European Society of Medical Oncology (ESMO), 11,12 there are evidence-based suggestions in order to harmonise the response evaluation and the management of patients with CML both in the upfront and salvage settings. In this issue of European Oncology and Haematology, Prof Hughes and Prof Saglio summarised the treatment options in patients with CML-CP who failed prior TKIs including alternative TKI treatments and allogeneic haematopoietic stem-cell transplantation (allo-HSCT), and then primarily focusing on a questionnaire which was completed by 14 physicians from different countries. 13 The purpose of the questionnaire and the subsequent paper was to understand the perspectives of the CML-treating physicians in the management of refractory CML-CP. The questionnaire had three sections. In the first section, the consensus responses to four questions mainly focusing on both BCR/ABL1-dependent and BCR/ABL1-independent resistance mechanisms; the difference in the rates of T315I mutation between daily practice and clinical trials; cross-intolerance between different TKIs; and solutions in order to address poor adherence to TKI treatment. The management of AEs, and patient education were also shared. 13 TOU CH MED ICA L MEDIA 15