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European Oncology & Haematology Highlights The Treatment of Chronic Myeloid Leukaemia (CML) in the Era of Tyrosine Kinase Inhibitors – What is New in the Battle of CML? Dilek Keskin 1 and Ahmet Emre Eskazan 2 1. Fellow of Hematology; 2. Associate Professor, Division of Hematology, Department of Internal Medicine, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey Abstract As the development of BCR-ABL1 targeting treatments has proceeded – first imatinib, then nilotinib and dasatinib – the treatment of chronic myeloid leukaemia (CML) has been revolutionised, and most patients live longer. Since tyrosine kinase inhibitors (TKIs) are expensive, generic imatinibs were introduced in order to overcome this matter. Allogeneic haematopoietic stem cell transplantation is still a treatment option in selected cases. Recent advances in targeting the CML stem cell suggested that this approach alone or together with TKIs could be an alternative therapeutic strategy for curing this disease. Keywords Allogeneic haematopoietic stem cell transplantation, bosutinib, chronic myeloid leukemia, dasatinib, generic, imatinib, nilotinib, ponatinib, tyrosine kinase inhibitor Disclosure: Dilek Keskin has no conflicts of interest to declare. Ahmet Emre Eskazan has received honorarium from Novartis. No funding was received in the publication of this article. 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: 16 May 2015 Accepted: 17 May 2015 Citation: European Oncology & Haematology, 2015;11(1):30–1 Correspondence: Ahmet Emre Eskazan, Istanbul University, Cerrahpasa Faculty of Medicine, Department of Internal Medicine, Division of Hematology, Istanbul, Turkey. E: As the development of BCR-ABL1 targeting treatments has continued, patients with chronic phase chronic myeloid leukaemia (CML‑CP) were shown to have similar survival rates in all age groups to that of general population in the era of tyrosine kinase inhibitors (TKIs). 1 First, imatinib and subsequently the second-generation TKIs (2GTKIs) (nilotinib and dasatinib) revolutionised the treatment of CML, and most patients live longer with usually improved quality of life than those treated before the era of TKIs. Currently TKIs are the mainstay of CML treatment, but some patients need additional treatment modalities due to resistance and intolerance to TKIs, and allogeneic haematopoietic stem cell transplantation (alloHSCT) is still a treatment option in selected cases. In addition, in most of the emerging nations where governments cannot afford the budget for the TKIs, physicians treating CML in these countries are advocating frontline alloHSCT. Also the high cost of new cancer drugs including those developed for CML is a major concern for healthcare payers, 2 especially in countries with restricted resources, so the governments most probably will have difficulties in affording the expenses of the original TKIs in the near future. In order to overcome this matter, generic imatinibs were introduced in the treatment of CML in many countries in the recent years. 3 Before the era of TKIs, CML therapy mainly consisted of hydroxyurea, busulphan, cytosine arabinoside and interferon-alpha (IFN-α). alloHSCT was the only modality to achieve long-term remission or cure in CML patients with good performance status and an available donor. Since the prospective, multicentre, open-label, phase III, randomised study – the International Randomized Study of Interferon and STI571 (IRIS) trial, 5 the natural history of CML significantly changed, and 10-year overall survival (OS) significantly increased from 10–20 to 80–90 %, 6 and imatinib is now the standard of care for newly diagnosed CML‑CP patients. Long- term follow-up of the IRIS trial showed that the responses achieved by imatinib were durable, but by the end of 8 years, 45 % of the patients had to quit receiving imatinib due to failure or intolerance. 7 Carella et al. also commented on the matter of adverse events (AEs), e.g. fluid retention, myalgia and fatigue being the most important AEs of imatinib therapy. 4 In order to improve the response rates achieved by imatinib, there were attempts by both increasing the dose of imatinib (i.e. to 800 mg/daily) or combining imatinib with pegylated IFN-α. Several studies for both of these treatment strategies showed conflicting results, 8 and the toxicities were the major problem in dose escalation and combination studies. In this issue of European Oncology & Haematology, Carella and colleagues evaluated the current situation of CML treatment and they also overviewed the future perspectives for ‘curing’ CML. 4 2GTKIs were first introduced to be utilised in patients who were resistant or intolerant to imatinib, and then with two phase III, randomised trials, Evaluating Nilotinib Efficacy and Safety in Clinic Trials Newly Diagnosed 160 Touch ME d ica l ME d ia