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Background. The target therapy have changed chronic myelogenous leukemia (CML) entity from life-threatening to potential curable disease. With the wide range of three generations of tyrosine kinase inhibitors (TKI) we could provide optimal response for the vast majority and switching to treatment free remission (TFR) to substantial proportion of patients. The new inspiration of improving CML treatment results had been got with developing of new class TKIs – STAMP inhibitors with other point of action. The clinical trials of first in class STAMP inhibitor – asciminib demonstrated very rapid and high response rates including deep molecular responses in first line of CML treatment. These data resulted to U. S. Food and Drug Administration approval of asciminib for adult patients with newly diagnosed CML in chronic phase. Despite the several second generation TKIs (TKI2) approved for the first line, the majority of newly diagnosed CML are treated with imatinib in routine clinical practice due to economic and safety considerations. Besides good survival and response rates imatinib treatment give possibility of switching to TFR only for minority of patients. We hypothesized that the high rate of deep molecular responses with asciminib treatment in first line could substantially increase the proportion of CML patient which could be tried to stop treatment in TFR settings. Aim. To compare the costs of imatinib and asciminib in the first-line of CML treatment with the use of TFR strategy. Materials and methods. We have used Markov chain approach to compare strategies of first-line CML treatment with imatinib or asciminib with switching to other TKIs in case of intolerance or inadequate response, followed by therapy discontinuation in cases of long-term deep molecular response. Input parameters for transition rates were selected from clinical trials (IRIS, ENESTnd, DASISION, ENACT, CA180013, STIM, FILMC group, 200, Euro-SKI, ASCEND-CML, ASC4FIRST), our own data and expert opinion. Since there is no data on the rate of successful TFR in patients receiving asciminib, we assumed that the success of treatment discontinuation in that case may be comparable to those for TKI2. Prices for consultations, laboratory monitoring and drugs were obtained from insurance programs and published contracts. We selected 800 newly diagnosed patients with CML in Russia per year as the model population. A time interval of 10 years was used. We attempted to estimate the cost of treatment per patient and the total budget burden on the entire national population of CML patients. The total cost included direct costs of diagnostic procedures for diagnosis, monitoring of residual disease effects, the cost of medications (TKIs and concomitant drugs for the treatment of complications), and allogeneic stem cell transplantation. We additionally conducted cost-effectiveness analyses of asciminib and imatinib separately for the costs of achieving successful therapy discontinuation and a comparative analysis of the two treatment regimens. Statistical methods included simulation models. Results. Rapid and deep molecular responses with asciminib treatment allows an attempt to discontinue therapy in 53.9 % of patients with possible success of final drug discontinuation in 34.0 %, imatinib has lower probabilities: 25.9 and 11.2 % of patients, respectively. The costs of treating one patient and the cumulative costs of diagnostics and therapy of CML at the national level are significantly higher in the case of using asciminib instead of imatinib in the first line of CML treatment. The ratio of the asciminib / imatinib strategies cost ratio over 10 years is 2.38 for one patient and 2.82 at the population level. At the same time, the costs per 1 % probability of successful therapy discontinuation were lower for asciminib (43,448 rubles) than for imatinib (55,472 rubles). The costs of an additional 1 % of therapy discontinuation success in a comparative analysis of asciminib and imatinib was assessed as 37,601 rubles per one patient for one year of treatment or 3,133 rubles per one month of treatment. Sensitivity analysis of the price ratios of imatinib and asciminib showed that parity (equal value of total costs for diagnostics and treatment of one CML patient for ten years) will be as follows: at the current cost of imatinib (8,119 rubles), the equal costs of asciminib is 34,260 rubles; for the proposed cost of asciminib (190,298 rubles), the equal cost of imatinib is 157,200 rubles. Conclusion. Pharmacoeconomic modeling of diagnostics and therapy of chronic myeloid leukemia can assess the budget burden and its future dynamics at the individual patient, group, and national levels. The results of modeling the use of imatinib and asciminib in the first-line CML therapy showed an almost three-fold higher probability of achieving successful treatment discontinuation, as well as lower costs per 1 % probability of successful TFR when using asciminib compared to imatinib. The results of such modelling can be used in decision making process for the national treatment standards development and budget allowance. There are many limitations of this study due to simulation and stipulation of some important input parameters.