Tyrosine kinase inhibitor treatment discontinuation in chronic myeloid leukemia: patient views

Abstract

Patients with chronic myeloid leukemia (CML) in deep molecular remission may discontinue tyrosine kinase inhibitor (TKI) treatment without relapse. The present study aims to gain insight into the views of CML patients on TKI treatment discontinuation and identify factors that are associated with their willingness to discontinue treatment. A cross-sectional study, among adult Dutch CML patients was conducted to assess willingness and their views on benefits of and concerns about discontinuation. A total of 185 patients participated of whom 76% were willing to discontinue TKI-treatment. Patients considered the absence of side effects the most important benefit whereas fear of disease recurrence was their most prominent concern. Adequate monitoring was the most important prerequisite for TKI-treatment discontinuation. However, ambiguity with respect to perquisites indicate that patients on long-term TKI treatment should be adequately informed both on the possibility to discontinue treatment and on its benefits, risks, and measures that address risks.

Thiazole Ring—A Biologically Active Scaffold

“…Based on literature data regarding the nature of bis-thiazole-DNA interaction [98][99][100][101][102][103][104] and also the fact that dasatinib, a second-generation tyrosine kinase inhibitor, has a bisthiazole moiety [105] and encouraging previous results [106,107], Turan-Zituni et al [108] synthesized new bis-thiazole derivatives (64a-j, Figure 25) as anticancer drugs. Compounds were tested against A549 human lung adenocarcinoma, C6 rat glioma, 5RP7 H-rasoncogene transformed rat embryonicfibroblast, and NIH/3T3 mouse embryonic fibroblast cell lines using MTT assay.…”

1,4-Naphthoquinone (CNN1) Induces Apoptosis through DNA Damage and Promotes Upregulation of H2AFX in Leukemia Multidrug Resistant Cell Line

“…Although an enormous therapeutic improvement has been demonstrated, there are still some patients that develop treatment resistance mechanisms in the course of disease, making the use with of TKIs ineffective [ 5 , 6 ]. In this scenario, the multidrug resistance (MDR) phenotype is well recognized in clinical practice and continues to be one of the major obstacles in CML treatment, especially in blast crisis [ 7 , 8 , 9 , 10 ].…”

“…Although an enormous therapeutic improvement has been demonstrated, there are still some patients that develop treatment resistance mechanisms in the course of disease, making the use with of TKIs ineffective [5,6]. In this scenario, the multidrug resistance (MDR) phenotype is well recognized in clinical practice and continues to be one of the major obstacles in CML treatment, especially in blast crisis [7][8][9][10]. Approximately 20-40% of CML patients treated with TKIs fail due to primary refractoriness (primary resistance), where patients exhibit lack of efficacy to TKIs from initiation of therapy, while secondary resistance (acquired) is defined as the loss of response [11][12][13][14].…”

Why are not all eligible chronic myeloid leukemia patients willing to attempt tyrosine kinase inhibitor discontinuation? A Czech nationwide analysis related to the TKI stopping trial HALF

“…However, little is known about how many truly eligible patients are unwilling to attempt TFR, the reasons for their decision and what factors are associated with their unwillingness to discontinue long-term therapy since the reports mentioned above have substantial limitations. The surveys were often conducted in a limited number of centres [ 3 , 6 – 8 ], focused on patients who are able to use internet tools [ 5 , 10 ], focused on more educated patients who are connected to patient supportive organisations [ 5 , 7 , 9 ], and usually not specifically focused on patients who fulfilled the criteria for TKI discontinuation [ 3 – 6 , 9 , 10 ].…”

“…In the same analysis, patients who refused TFR attempts were more properly informed about the generic risk of relapse after TFR than patients willing to stop [ 8 ]. Furthermore, the impact of proper perception of relapse on patient decisions was supported by an adverse relationship between increasing willingness to attempt TFR and decreasing hypothetical risk of relapse [ 3 , 9 ]. Similarly, the importance of accurate information, including adequate relapse perception, was emphasised by Saglio et al in a unique joint patient‒physician perspective on TFR [ 11 ].…”