Pb1978: patient-centredness is pivotal in a prospective dose reduction trial of tyrosine kinase inhibitors in patients with chronic myeloid leukaemia

Topic: 8. Chronic myeloid leukemia - Clinical Background: Dose reduction of tyrosine kinase inhibitors (TKI) for patients with chronic myeloid leukaemia (CML) can reduce adverse drug events and medication costs while maintaining therapeutic effectiveness. Aims: This study aims to develop and evaluate a patient-guided dose reduction strategy, consisting of a patient-decision aid to guide decision making and a shared decision-making consultation to discuss patient’s willingness for dose reduction and to define a personalized dose. Methods: We developed, pilot-tested and evaluated a complex intervention guided by Medical Research Council framework. Phase 1 involved intervention development based on a needs assessment using semi-structured interviews with 19 CML patients and 12 healthcare providers regarding dose reduction. In a separate iterative design process with 18 patients and 16 healthcare providers a decision aid was developed. In phase 2 the intervention was pilot-tested on acceptability, feasibility and delivery method with 6 patients and 3 healthcare providers. Phase 3 is a prospective, multicentre, single-arm trial with 147 CML patients with stable disease assessing intervention effectiveness of dose reduction on the proportion of patients with intervention failure, defined as loss of major molecular response, at 12 months after dose reduction. Secondary outcomes include validated PROMs for side effects, quality of life, medication adherence and beliefs. Interim analysis is planned for 70 patients 6-month follow-up.* Results: Patients and healthcare providers expressed a need for dose reduction and developed together a patient decision aid to guide shared decision-making. Pilot-testing showed intervention acceptance and feasible recruiting and delivery process. Currently phase 3 is ongoing in 9 Dutch hospitals, with 80 CML patients who provided consent and received a personalised TKI dose. Preliminary results showed 3/15 (20%) patients with intervention failure after dose reduction at 6-month follow-up. Summary/Conclusion: Patient-directed dose reduction using shared decision-making personalizes TKI management without loss of effectiveness. *Interim analysis data will be presented during conference Keywords: Tyrosine kinase inhibitor, Chronic myeloid leukemia, Dose escalation, Side effects