OBJECTIVES: TKI treatment is the standard of care in CML. Currently, guidelines recommend that patients who respond to TKI treatment continue indefinitely. However, an alternative therapeutic approach to discontinue TKI treatment in patients who have achieved and sustained a deep molecular response (MR), has been under investigation for several years. The objective of this study was to develop a model to evaluate the clinical and economic impact of implementing TFR in patients with Ph+ CML-CP treated with imatinib and nilotinib in 1L. METHODS: A five-year medical-economic model was developed from the French national perspective to assess the impact of TFR in prevalent and newly diagnosed 1L TKI patients. TKI treatment was discontinued in patients who were treated for at least 3 years with the same TKI and had reached and maintained a deep MR (MR ≥ 4) for the last 2 years (market research and ENESTnd). TKI treatment was resumed in case of loss of major MR (MR<3). Model assumed a 60% relapse rate (STIM) for either TKI. French clinical experts validated the model clinical framework, inputs and assumptions. RESULTS: The model estimates that between 2016 and 2020, 2,606 patients will become eligible for TFR, more than half (1,433) will remain in TFR. Mainly prevalent imatinib and newly diagnosed nilotinib patients are eligible for TFR, due to large prevalent imatinib population and high MR on 1L nilotinib. The cumulative net savings over the five-year period are expected to be €126.6 million. A small increase of monitoring costs is expected, with increased frequency of physician visits and molecular testing upon TFR initiation. CONCLUSIONS: The model can be used to inform healthcare decision makers on the importance of TFR and the potential savings. The model inputs will be updated with the upcoming publications of the nilotnib TFR clinical trial results (ENESTFreedom).