Quality‐of‐life, mental health, and perspective on TKI dose reduction as a prelude to discontinuation in chronic phase chronic myeloid leukemia

Abstract

BackgroundTreatment‐free remission (TFR) has become the main target for chronic myeloid leukemia (CML). Tyrosine kinase inhibitors (TKI) dose optimization is crucial in managing adverse events, and improving adherence in clinical practice. In persons achieving a deep molecular response (DMR), some data suggest TKI dose reduction before discontinuation does not change success rate of achieving TFR, but this is controversial. However, data on quality‐of‐life (QoL) and mental health in CML patients with full‐dose TKI, low‐dose TKI, and TKI discontinuation are limited. Moreover, recent evidence indicating the feasibility of TKI dose reduction and discontinuation after dose reduction, which may change CML patients' perspectives on TKI discontinuation.MethodsWe conducted a cross‐sectional study using online questionnaires to explore the QoL, mental health in patients with diverse TKI dose, and perspective on TKI dose reduction as a prelude to discontinuation.Results1450 responses were included in the analysis. 44.3% of respondents reported a moderate‐to‐severe impact of TKI treatment on their QoL. 17% of respondents had moderate‐to‐severe anxiety. 24.4% of respondents had moderate‐to‐severe depression. In 1326 patients who had not discontinued their medication, 1055 (79.6%) patients reported they would try TKI discontinuation because of concerns over side effects of long‐term medication (67.9%), financial burden (68.7%), poor QoL (77.9%), pregnancy needs (11.6%), anxiety and depression while taking TKI (20.8%), inconvenience of TKI treatment (22.2%). 613 of 817 (75.0%) patients on full‐dose TKI therapy indicated they preferred trying a dose reduction before discontinuing TKI therapy after dose reduction compared with 31 (3.8%) preferring no dose reduction before stopping.ConclusionsTKI dose reduction showed a significant improvement of patients' QoL and mental health, comparable to the effect of TKI discontinuation. Most patients indicated they preferred dose reduction before stopping TKI therapy. In clinical practice, TKI dose reduction can be considered as a bridge from full‐dose treatment to discontinuation.Our results showed that tyrosine kinase inhibitors (TKI) dose reduction showed a significant improvement of patients' quality‐of‐life and mental health, comparable to the effect of TKI discontinuation. Most patients desire to discontinue TKI in the future. TKI discontinuation after dose reduction is more acceptable compared to discontinuing it directly. In clinical practice, TKI dose reduction can be considered as a bridge from full‐dose treatment to discontinuation. Please do not hesitate to contact me in case further clarification is needed with this submission.

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

“…The results of multivariate analysis revealed significant differences between both cohorts, with greater proportion of female patients, patients treated with the last TKI longer, patients with longer travel times to the centre and patients with lower levels of education in the Anti-HALF cohort. These findings were mostly inconsistent with previously reported results (Supplementary Table S3 ) [ 3 , 5 – 7 , 9 , 10 ]. Nevertheless, paid employment [ 9 ] and younger age [ 5 , 6 ] as factors supporting willingness to attempt TFR were in line with our findings, with Anti-HALF patients being older and more frequently unemployed or retired than HALF participants.…”

“…In our nationwide CML patient cohort, 56 out of 246 (22.8%) TFR candidates were not willing to stop TKI treatment in a controlled manner. The most frequently reported reasons for reluctance to attempt TFR in our survey align with previously published data (Supplementary Table S1 ) [ 3 – 10 ]. Villemagne Sanchez et al emphasised, that this reluctance was often associated with a need for additional information or an incomplete understanding [ 7 ].…”

“…Among others, a nonnegligible proportion of patients reported fear, anxiety, or depression both during TFR and when they had to reinitiate TKI therapy [ 2 ]. Similar negative feelings are frequently mentioned in the context of the decision to not stop TKI treatment; furthermore, a considerable proportion of patients (17–50%) have been reported to be unwilling to attempt TFR [ 3 – 10 ] (Supplementary Table S1 ). 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.…”

“…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 our study, we adopted a gradual dose reduction concept before treatment cessation to enhance patient acceptance, among other objectives. Although the results of the HALF trial have not yet been analysed, recently published data from a large Chinese survey indicated a notable preference to reduce the dose before TFR attempt in 613/817 (75%) patients versus 31/817 (3.8%) patients who preferred no dose reduction before stopping [ 10 ].…”