Modifiable determinants of adherence to tyrosine kinase inhibitors in classical myeloproliferative neoplasms: A mixed-methods systematic review protocol

Introduction: Non-receptor Tyrosine kinase inhibitors (TKIs), such as ABL1 and JAK inhibitors, are central to the management of classical myeloproliferative neoplasms (MPNs), yet non-adherence remains frequent and is associated with poorer clinical outcomes. Although adherence-related factors have been explored, the evidence has not been systematically synthesised within a behavioural theory framework to guide the development of effective interventions. This review aims to synthesise evidence on modifiable determinants (barriers and facilitators) influencing adherence to TKI therapy in adults with classical MPNs, and to classify these determinants using the Theoretical Domains Framework (TDF) and Capability, Opportunity, Motivation-Behaviour (COM-B) model. Methods: This is a mixed-methods systematic review protocol. We will search MEDLINE/PubMed, Embase, CINAHL, LILACS, PsycINFO, and the Cochrane Library from inception to the present, without date restrictions, alongside grey literature sources (OpenGrey, WorldCat, and Google Scholar). Key terms will include myeloproliferative neoplasms, chronic myeloid leukaemia, polycythaemia vera, primary myelofibrosis, tyrosine kinase inhibitors, imatinib, dasatinib, ruxolitinib, and medication adherence. Two reviewers will independently screen studies, extract data, and assess methodological quality using design-appropriate appraisal tools. Quantitative findings will be synthesised narratively and meta-analysed where appropriate. Effect estimates from quantitative studies and qualitative findings (including participant quotations and interpretative data) will be mapped to TDF domains and COM-B components. A mixed-methods synthesis will integrate and triangulate determinants across study designs. Confidence in the evidence will be assessed using GRADE (quantitative) and CERQual (qualitative). Conclusion: This review will provide a theory-informed synthesis of modifiable determinants of TKI adherence in classical MPNs, supporting the identification of targets for future adherence-enhancing interventions. Trial registration: Systematic review registration: PROSPERO registration number: CRD42024512635.