Frontline TKI Strategies for Chronic Myeloid Leukemia Patients: Balancing Outcomes and Costs in Pursuit of Treatment-Free Remission and Dose Reduction

OBJECTIVES: Chronic myeloid leukemia (CML) management now includes dose reduction (DR) and treatment-free remission (TFR) to increase survival and limit adverse effects. Imatinib has thus far been the most cost-effective frontline tyrosine kinase inhibitor (TKI). Prior cost-effectiveness evaluations have addressed TFR, but omitted DR, various adult age groups and anticipated second-generation (2G) TKIs cost reductions resulting from patent expirations. This study provides a comprehensive evaluation by incorporating these factors.

METHODS: A Markov model using 17 health states evaluates the most cost-effective frontline TKI for newly diagnosed adult CML chronic phase patients, incorporating TFR, DR and 2GTKI patent expiration. Transition probabilities, costs and utilities were derived from literature data. Incremental cost-effectiveness ratios (ICERs) were calculated. Sensitivity analysis and model validation were conducted.

RESULTS: Nilotinib is most effective (20·13 QALYs) and imatinib is least effective (17·25 QALYs) in base case analysis. Imatinib has a high probability of being cost-effective compared to dasatinib (89·80%), nilotinib (62·70%) and bosutinib (78·40%) at a WTP of €80,000/QALY. Including DR only, imatinib is considered cost-effective compared to dasatinib (97·70%), bosutinib (97·60%) and nilotinib (74·90%). For patients at age 70, imatinib has a probability of being cost-effective of 99·40%, 93·60% and 97·80% compared to dasatinib, nilotinib and bosutinib. With a 50% 2GTKI cost reduction, nilotinib is considered cost-effective compared to imatinib (98·40%), dasatinib (94·80%) and bosutinib (68·90%).

CONCLUSIONS: 2GTKIs excel in yielding QALYs, for adult and older (age >70) patients. Nevertheless, given current TKI prices, imatinib remains cost-effective. Including DR and TFR generates more QALYs, slightly increasing the probability of 2GTKIs being cost-effective. Cost reductions due to expected patent expirations of 2GTKIs greatly increase this probability. These findings could significantly impact the management of CML and patient-centered decision-making for frontline TKIs, as well as guide discussions on cost considerations once patents for 2GTKIs expire.