Search

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]