OBJECTIVES: Despite the improved effectiveness and safety of novel therapies, the rising cost of cancer drugs poses a significant challenge to healthcare decision-makers. The goal of this research is to model how strategies aiming to achieve treatment-free remissions (TFR) will impact the outcomes and treatment costs of patients with chronic myeloid leukemia (CML). METHODS:  A model was created to assess how many patients treated with imatinib and nilotinib would be eligible to stop treatment after achieving a sustained deep molecular response (DMR). Efficacy and discontinuation rates for imatinib and nilotinib were retrieved from ENESTnd and ENEST1st, while TFR data was obtained from STIM, EuroSKI and ENESTfreedom. The costs were calculated for the relevant outcomes for each strategy. RESULTS: After excluding patients who discontinue treatment due to intolerance or failure, the rates of MR4.0 and MR4.5 after 2 years of treatment are estimated to be 11.39% and 6.0% for imatinib, and 44.66% and 31.2% for nilotinib. Using the design of Euro-SKI and ENESTfreedom (patients eligible to stop treatment after 3 years of therapy with at least 1 year of DMR) and the annual incidence of 110 CML patients in Portugal, our model estimates that successful discontinuation of treatment might be achieved for 6 and 28 patients treated with imatinib and nilotinib, respectively. In a setting where the price of imatinib becomes 30% lower, the monthly costs of a nilotinib-based strategy become lower after 3.5 years. Alternative scenarios tested the impact of longer treatment/maintenance times and lower imatinib prices. CONCLUSIONS:  Despite the limited data available, this model provides a useful framework to demonstrate that in a 4 years’ time horizon, the cost of nilotinib-based strategies might become efficient alternatives for the relevant outcomes (DMR and TFR). Besides the direct savings obtained by effective treatment discontinuation, significant gains in quality of life should be accounted for.