Jaké dávky inhibitorů tyrozinkináz jsou v léčbě pacientů s chronickou myeloidní leukemií optimální?
|Title in English||What is the optimal dose of tyrosine kinase inhibitors in chronic myeloid leukaemia?|
|Year of publication||2021|
|Type||Article in Periodical|
|Magazine / Source||Transfuze a hematologie dnes|
|MU Faculty or unit|
|Keywords||chronic myeloid leukaemia; Tyrosine kinase inhibitors; dose reduction; intermittent dosing|
|Description||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.|