Association between proton pump inhibitor co-medication and treatment switching in dasatinib-treated patients with chronic myeloid leukemia: a German real-world evidence study

Dasatinib absorption is pH-dependent, and concomitant use of Proton Pump Inhibitors (PPIs) can substantially reduce dasatinib exposure. Whether this interaction has clinical relevance and affects treatment outcomes in patients with chronic myeloid leukemia (CML) remains unclear. This retrospective cohort study used German statutory health insurance claims data (2010 - 2024). Adults with CML who initiated dasatinib treatment were selected. Patients were classified according to concomitant PPI use around dasatinib initiation. The primary endpoint was time to switch to another systemic CML therapy. Two analytical cohorts were evaluated (incident and prevalent cohorts). Propensity score matching and Cox proportional hazards models were used to compare patients with and without PPI co-medication. Sensitivity analyses censored follow-up at severe adverse events and restricted the population to users of the originator dasatinib formulation. Among 297 dasatinib patients in the incident and 372 in the prevalent cohort, PPI co-medication was observed in approximately 19-21% of patients. After matching, concomitant PPI use was consistently associated with earlier treatment switching. This association reached statistical significance in the prevalent cohort (hazard ratio: 1.87, 95% CI 1.18-2.95; p = .008) and was directionally consistent in the incident cohort. Sensitivity analyses yielded directionally consistent findings. In this large real-world analysis, concomitant PPI use was associated with earlier treatment switching in dasatinib-treated patients with CML. While causality cannot be established, these findings are consistent with the known pH-dependent interaction and reinforce existing recommendations to avoid PPI co-medication during dasatinib therapy whenever feasible.