Ensuring adherence to Tyrosine Kinase Inhibitors (TKI) therapy is crucial for Chronic Myeloid Leukemia’s (CML) treatment success. Vigilant monitoring allows early detection of treatment failures enabling prompt medication adjustments. This underscores a major challenge in managing TKI therapy for CML patients, given that the minimum adherence rate required for maintaining a satisfactory response remains unclear.

Thus, this systematic review aims to answer the question: what is the minimal adherence rate needed for patients with BCR::ABL1 positive CML undergoing TKI therapy to achieve a satisfactory molecular response?

Therefore, a systematic review is being conducted following the PRISMA guideline and Cochrane Handbook. The protocol was registered on PROSPERO (CRD42024558338). The research question, eligibility criteria, and search strategy were established using the PICOS acronym. The search strategies were applied on PubMed (MEDLINE), Scopus, Embase, Web of Science, and Cochrane Central Register of Controlled Trials. The publication date was restricted to 1998 and later, as the first clinical trial investigating TKI therapy in CML was initiated from that year onward. The initial search was conducted on 24 May 2024 and will be updated prior to the narrative synthesis. The study selection was performed through blinded peer review using Rayyan QCRI®. A third reviewer (a topic expertise) solved the discrepancies. At this time, three independent reviewers are conducting the data extraction using a standard Excel® table and, after that, the expertises will validate the data extracted. The risk of bias and overall quality of evidence will be evaluated after data extraction. A narrative synthesis of the findings will be provided. A meta-analysis will be conducted if a minimum of three comparable studies is found.

A total of 10,054 records were identified. After removal of duplicates, 6,595 records remained for title and abstract screening. 114 studies were selected for full-text screening. Of these, four were unavailable. Ultimately, 32 studies met the eligibility criteria and were included for data extraction. Until now 25 studies were extracted. Observational studies were the leading study design. The most frequent adherence measurement methods were pill count, variations of the Morisky Medication Adherence Scale questionnaire, Medication Event Monitoring System, and Medication Possession Ratio. Most studies enrolled patients in the chronic phase. The main criteria for the evaluation of clinical outcomes was the European Leukemia Net Guidelines. Countries were diverse, including nations across different income strata. So far, studies have indicated that adherence is strongly associated with better major molecular response, complete cytogenetic response and event-free survival, being higher adherence rates (≥ 85%) consistently linked to superior clinical outcomes. Adverse effects and treatment intolerance were commonly reported as key contributors to non-adherence, leading patients to discontinuation. At the end of this study, it is expected to establish a clear threshold for adherence to TKI therapy that correlates with a satisfactory molecular response in patients with CML, ultimately enhancing monitoring strategies to improve patient outcomes.