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The introduction of the first tyrosine kinase inhibitor imatinib into clinical practice has been associated with dramatical change in chronic myeloid leukaemia treatment over the past 20 years. It represents one of the biggest achievements in haematology and oncology per se. Imatinib was followed by second- and third generation tyrosine kinase inhibitors (nilotinib, dasatinib, bosutinib and ponatinib) resulting in newly dia­gnosed chronic myeloid leukaemia patients having almost the same life expectancy as the general population. Nevertheless, this often-lifelong treatment can be associated with side effects, which in extraordinary cases may be life threatening. Vascular adverse events are also included among such serious adverse events and their incidence varies over a wide range from 0.32–47.8%, most frequently in association with nilotinib or ponatinib treatment. Their incidence in daily clinical practice in the Czech Republic was evaluated in a retrospective analysis of the INFINITY database. From January 2005 to August 2020, chronic myeloid leukaemia was dia­gnosed in 1029 patients, with 1007 having valid records for analysis. Of these, 964 patients were in chronic phase. At least one vascular adverse event occurred in 82 patients (8.5%) in chronic phase during tyrosine kinase inhibitors therapy, most frequently in patients receiving nilotinib (10.8%) and ponatinib (8.3%). During first-line tyrosine kinase inhibitor treatment, 60 patients (6.3%) experienced at least one vascular adverse event. In direct comparison of first line imatinib and nilotinib therapy, we found a significantly higher incidence of cardiovascular (2.6 vs. 7.2%; P = 0.013), cerebrovascular (1.4 vs. 4.8%; P = 0.019), and peripheral vascular adverse events (0.2 vs. 4.0%; P = 0.001) in nilotinib treated patients, respectively. This paper offers a more detailed overview of vascular adverse event incidence in patients with chronic myeloid leukaemia treated with tyrosine kinase inhibitors in clinical practice in the Czech Republic and its comparison with available literature. [ABSTRACT FROM AUTHOR]

Dasatinib is a potent tyrosine kinase inhibitor of not only Bcr-Abl1, but also of the Src kinase family, c-kit and PDGFR-â. This "off-target" effect is the probable cause of pleural effusions, which complicate dasatinib therapy in about one third of patients. The following case report describes a chronic myeloid leukaemia patient with not only recurrent pleural effusions but also pulmonary arterial hypertension as a serious adverse event leading to dasatinib discontinuation. [ABSTRACT FROM AUTHOR]

The introduction of tyrosine kinase inhibitors (TKI) has significantly improved the prognosis of chronic myeloid leukaemia (CML) patients and prolonged their life expectancy near to that of the global population. However, long-lasting or even lifelong therapy carries a risk of side effects, quality of life impairment, high financial costs and also psychological concerns regarding the ever-present underlying cancer. Long-time therapy discontinuation with treatment-free remission (TFR) achievement became a new goal in CML treatment, but unfortunately could be achieved in only a minority of patients. Thus, increasing attention has focused on long-term therapy optimization, particularly in terms of TKI dose reduction or intermittent administration in order to improve tolerance and maintain efficacy. Originally recommended TKI standard doses based on pharmacokinetics and pharmacodynamics studies were already modified in several cases during subsequent clinical trials mainly due to increasing evidence of treatment safety. An effort to further decrease TKI doses or use intermittent dosing has been supported by favourable published data, or has been a subject of ongoing clinical trials including dose reductions prior to a TFR attempt. TKI dose reduction consideration has also been included in the new European LeukemiaNet recommendations for treating CML. In this manuscript, a comprehensive review of TKI dose optimization attempts is offered in the broader context of recommended standard TKI doses evolution and increasing pharmacokinetics knowledge. [ABSTRACT FROM AUTHOR]

The introduction of tyrosine kinase inhibitors into clinical practice led to dramatic improvement of chronic myeloid leukaemia patient prognosis. The life expectancy of newly diagnosed chronic myeloid leukaemia patients is almost the same as that of the general population, a unique feature not only in haematology but also in oncology per se. However, in the case of many patients this is offset by the need for long-term, lifelong pharmacotherapy with all its negative consequences such as side effects, economic burden and pregnancy planning restriction. Adverse events may negatively affect patient quality of life, restrict routine daily activities and serious events associated especially with second and third generation tyrosine kinase inhibitors may even prove life-threatening. Depending on the TKI selected, 30-50% of patients achieve a deep molecular response. In individuals with stable deep molecular response, tyrosine kinase inhibitor discontinuation and subsequent treatment-free remission maintenance have become the new goal of CML treatment. Although treatment-free remission may be associated with some drawbacks such as withdrawal syndrome and a degree of late relapse risk, it definitely represents a relatively safe alternative to long-term therapy and is now proceeding from clinical trials into daily clinical practice. This article summarizes comprehensively clinical trials focused on treatment-free remission in CML patients, including their implications for daily clinical practice and potential consequences of tyrosine kinase inhibitors cessation. [ABSTRACT FROM AUTHOR]