OBJECTIVES: Tyrosine kinase inhibitors (TKIs) account for the vast majority of healthcare expenditure on patients with chronic myeloid leukemia (CML), and it has been demonstrated that TKI discontinuation in patients in long-term deep molecular remission (DMR) is safe and improves quality of life. Our objective was to estimate the budget impact of TKI discontinuation in CML patients in long-term DMR from the perspective of the French healthcare system. METHODS: This analysis was conducted over a 5-year time horizon using a Markov model with cycles of 6 months. Transition probabilities were estimated through systematic reviews and meta-analyses. Costs were estimated from the French National Claims Database. Monte Carlo simulations were performed to take into account the uncertainty surrounding model parameters. Sensitivity analyses were carried out by varying the size of the target population and the cost of TKIs. RESULTS: Over a 5-year period and for a target population of 100 patients each year eligible and agreeing to stop TKI, the TKI discontinuation strategy would save €25.5 million (95% confidence interval -39.3 to 70.0). In this model, the probability that TKI discontinuation would be more expensive than TKI continuation was 12.0%. In sensitivity analyses, mean savings ranged from €14.9 million to €62.9 million. CONCLUSIONS: This study provides transparent, reproducible, and interpretable results for healthcare professionals and policy makers. Our results clearly show that innovative healthcare strategies can benefit both the healthcare system and patients. Savings from generalizing TKI discontinuation in CML patients in sustained DMR should yield health gains for other patients.< Réduire