Updated Cost-Effectiveness Analysis of First-Line Imatinib Compared to Interferon-α in Patients with Newly Diagnosed Chronic Myeloid Leukemia in the Chronic Phase Using 60-Month Data from IRIS.
Authors: Reed Shelby D. , Anstrom Kevin J. , Li Yanhong , Schulman Kevin A. 
Published: October 2019

Abstract
Background: Our previous cost-effectiveness analysis of first-line imatinib versus interferon- plus low-dose cytarabine in newly diagnosed patients with CML in the chronic phase was based on a median of 19 months of follow-up from the International Randomized Study of Interferon- (IFN) vs. STI571 (imatinib) (IRIS).
Objective: With 60 months of follow-up data now available, we had the opportunity to update our cost-effectiveness analysis.
Methods: To update the analysis, we calibrated the survival curves generated with the original cost-effectiveness model to the survival curves generated with the empirical 60-month data from IRIS for patients randomized to treatment with imatinib. Due to the high rate of crossover among patients randomized to IFN in IRIS, we relied on historical data to model survival estimates for patients treated with IFN. We updated costs to 2006 values. Two sets of costs were applied to imatinib and IFN: average wholesale prices (AWP) and wholesale acquisition costs (WAC).
Results: The 60-month IRIS data revealed that observed survival for patients randomized to imatinib was better than predicted in our original analysis. 89.4% of IRIS patients initially randomized to imatinib were still alive at 5 years compared to a projection of 83.2% with the previously modeled estimates. When stratifying according to the attainment of a complete cytogenetic response (CCyR), patients with or without a CCyR among those randomized to imatinib had better survival than the historical cohorts of CCyR and non-CCyR patients used in our initial analysis, demonstrating that our previous estimates of survival benefit with imatinib were conservative. We calibrated the model by decreasing the hazard rates for death for patients with and without CCyR by 37% for the imatinib group. After updating the cost-effectiveness model, remaining life expectancy was estimated at 19.0 years for patients treated with first-line imatinib, an increase of 3.7 years over the original analysis. When adjusting for quality of life, 15.6 QALYs were estimated for the imatinib group, an increase of 3.5 QALYs compared to the original analysis. When AWPs were applied to imatinib and IFN, incremental cost-effectiveness ratios (ICERs) ranged from $51,800 to $57,500 per QALY when applying less and more conservative assumptions about the duration of treatment with imatinib. When WACs were applied, ICERs ranged from $42,000 per QALY to $46,200 per QALY. The updated ratios using AWPs were generally higher than the original estimate of $43,300 per QALY and the updated ratios using WACs were consistent with the original estimate. These results occurred despite the gain in QALYs due to higher acquisition costs of medications and the close tracking of increased survival and increased costs. Sensitivity analyses revealed that the ICERs were most sensitive to the costs of imatinib and IFN.
Conclusion: As demonstrated with the 60-month data, it appears that our original survival estimates were conservative. Updated estimates of survival gain with imatinib increased by 3.7 years over the original model. Variation in the cost-effectiveness of first-line imatinib was more closely associated with changes in medication costs than changes in expected survival benefit, most of which has yet to be observed.