Prognostic factors for successful discontinuation of tyrosine kinase inhibitor treatment in patients with chronic myeloid leukemia
Tomashevska N.Y.1, Kotlyarchuk K.B.2, Korolchuk O.S.3, Boyko O.I.2, Maslyak Z.V.2
- 1State Non-profit Enterprise «Danylo Halytsky National Medical University in Lviv», Ukraine
- 2State Institution «Institute of Blood Pathology and Transfusion Medicine of National Academy of Medical Sciences of Ukraine», Lviv, Ukraine
- 3Municipal Non-profit Enterprise «Lviv Territorial Medical Association «Clinical hospital of planned treatment, rehabilitation and palliative care», Ukraine
Summary. The purpose of the study was to analyse the literature to study current views on monitoring the results of treatment with tyrosine kinase inhibitors in patients with chronic myeloid leukaemia and to determine the criteria for successful discontinuation of therapy. Materials and methods. The study used analytical and bibliosemantic methods. The main publications describing the current principles of monitoring the response to treatment of patients with chronic phase chronic myeloid leukaemia, searching for criteria for safe discontinuation of therapy after achieving a molecular response and predicting the likelihood of relapse after discontinuation of tyrosine kinase inhibitors were analysed. We selected 47 primary sources that most fully reflect these views. Results and conclusions. Chronic myeloid leukaemia is defined by a unique molecular feature, the BCR-ABL1 oncogene. Decades of research on the role of BCR-ABL1 kinase in the pathogenesis of chronic myeloid leukaemia have resulted in the development of highly effective therapeutic agents targeting the oncogenic kinase activity of BCR-ABL1. For many patients with chronic myeloid leukaemia, tyrosine kinase inhibitors have turned a previously fatal disease into a completely curable one and have shown long-term survival results. It has been established that approximately half of patients in long-term remission without treatment can maintain a molecular response without continuing therapy with tyrosine kinase inhibitors. However, little is known about whether treatment can be safely discontinued in the long term. Various clinical trials are investigating eligibility criteria for predicting safe discontinuation of imatinib or the second-generation tyrosine kinase inhibitors dasatinib or nilotinib. It remains unclear why some patients lose their molecular response shortly after discontinuation of therapy. Various hypotheses are being considered, including the state of the immune system and the persistence of residual leukaemic stem cells. Despite the remaining questions, the decision to continue or discontinue therapy, achieving molecular remission and maintaining remission without treatment has become a priority for clinicians treating patients with chronic myeloid leukaemia. For today, the identification of the BCR-ABL1 transcript is crucial for both the diagnosis of chronic myeloid leukaemia and the monitoring of minimal residual disease. The effectiveness of other monitoring methods based on RNA, DNA and protein analysis are also being tested. A better understanding of relapse mechanisms will allow us to develop prognostic factors and identify optimal candidates for successful therapy discontinuation.
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