Predictive indicators of successful tyrosine kinase inhibitor discontinuation in patients with chronic myeloid leukemia

Abstract

Clinical trials have demonstrated that some patients with chronic myeloid leukemia (CML) treated for several years with tyrosine kinase inhibitors (TKIs) who have maintained a molecular response can successfully discontinue treatment without relapsing. Treatment free remission (TFR) can be reached by approximately 50% of patients who discontinue. Despite having similar levels of deep molecular response and an identical duration of treatment, the factors that influence the successful discontinuation of CML patients remain to be determined. In this review we will explore the factors identified to date that can help predict whether a patient will successfully achieve TFR. We will also discuss the need for the identification of predictive biomarkers associated with a high probability of achieving TFR for the future personalized identification of patients who are suitable for the discontinuation of TKI treatment.

Keywords: Biomarkers; Tyrosine kinase inhibitors; Treatment discontinuation; Molecular monitoring; Duration of therapy; Leukemia; Myelogenous; Chronic; BCR-ABL positive

Core Tip: Clinical trials have shown that approximately 50% of patients with chronic myeloid leukemia who reach a deep molecular response (MR) following treatment for several years with tyrosine kinase inhibitors (TKI) can discontinue and remain in treatment-free remission (TFR). Factors such as the duration of TKI treatment and duration and depth of the patient’s MR prior to discontinuation appear to be important in determining whether TFR is achieved. However, it is clear that other biological factors must determine whether an individual will remain in TFR after discontinuation. Future studies should aim to elucidate biomarkers predictive of TFR.