OBJECTIVES: To assess treatment cost and duration (months) of major cytogenetic response (MCyR) using ponatinib in patients intolerant or resistant to 2G TKI, compared to treating with only 2G TKIs, in patients with Ph+ leukemia, in Italy. METHODS: A 3-year Markov model with 1-year cycles simulated patients with Ph+ leukemia to estimate outcomes in those eligible for ponatinib therapy, defined as 1) 2G TKI-resistant, 2) 2G TKI-intolerant if imatinib is not clinically appropriate, or 3) with T315I mutation. Eligible patients received treatment sequences including 2G TKIs and ponatinib in the ponatinib arm and 2G TKI only in the comparator arm. Patients without MCyR by 12 months were switched to the next therapy line until TKI options were exhausted, then to best supportive care. MCyR rates for 2G TKI or ponatinib were estimated from clinical trial data and expert opinion. Patients were assumed to accrue MCyR months until estimated treatment failure. Monthly treatment costs reflect approved EU dosing and list prices; cost of ponatinib was assumed equivalent to the US. RESULTS: We estimated 184, 280, and 360 ponatinib-eligible patients in years 1-3, respectively. Treating ponatinib-eligible Ph+ leukemia patients with 2G TKIs yielded a 3-year cost of €58.51 million and a total of 2,536 months in MCyR, at an average cost of €23,068/MCyR month. Using ponatinib in eligible patients cost €79.54 million and provided 5,649 months in MCyR, at an average cost of €14,079/MCyR month. CONCLUSIONS: The treatment strategy including ponatinib provided more than double (2.2-fold) the MCyR months at 36% higher cost compared to the 2G TKI strategy. The average cost/MCyR month with ponatinib was lower than the average cost/MCyR month with 2G TKIs. While there are limitations with the methology and assumptions of the model, this analysis suggests treatment with ponatinib may provide good value for ponatinib-eligible Italian patients.