Discontinuation of tyrosine kinase inhibitors in chronic myeloid leukemia patients – worldwide battlefield

Abstract

Advances in understanding the pathogenesis of chronic myeloid leukemia (CML) and implementation of the therapy with tyrosine kinase inhibitors (TKI) could be considered as a prototype of successful fight against cancer. However, for an optimally responding patient it is recommended to follow the TKI therapy indefinitely. The question about the possibility of safe TKI treatment discontinuation in certain clinical situations was raised and is currently under close investigation worldwide. Currently, imatinib discontinuation trails have shown that about 60% of eligible patients experienced molecular recurrence within 6 months of treatment discontinuation, while the remaining 40% remained in defined deep molecular response throughout the duration of mostly two years follow-up. Interestingly, retreatment with the same TKI or another TKI was successful in the vast majority of patients demonstrating molecular recurrence of the disease. These findings support the concept of safe TKI treatment discontinuation and its usefulness for a specific subset of CML patients. However, recent data are not sufficient for TKI discontinuation attempts outside clinical trials yet. Because of the high risk of potentially problematic molecular recurrences of the pathological clones, the key question is to find the right predictive marker of TKI discontinuation success, however it stays unsolved yet. This minireview brings a concise summary of this hot topic with a realistic view from clinical routine.

Cancer Management by Tyrosine Kinase Inhibitors: Efficacy, Limitation, and Future Strategies

“…Many studies are thus working on the possibility of discontinuing TKI therapy after a certain response is achieved. Some researches have identified specific subsets of patient populations which could consider discontinuation of TKIs [182].…”

CML as Part of Dual Malignancies—A Retrospective Analysis: Possible Mechanisms and Review of Literature

“…The natural history of disease has been significantly modified post introduction of tyrosine kinase inhibitors (TKI's) therapy with many patients having near normal survival [4]. The present guidelines still suggest lifelong therapy for CML with few ongoing discontinuation trials [5][6][7][8][9]. Concurrently, TKI's have lately been implicated in other immunemodulatory and immunosuppressive effects by acting through T cells [10][11][12].…”