Cost-effectiveness of Tyrosine Kinase Inhibitor Treatment Strategies for Chronic Myeloid Leukemia in Chronic Phase After Generic Entry of Imatinib in the United States

Abstract

Background: We analyzed the cost-effectiveness of treating incident chronic myeloid leukemia in chronic phase (CML-CP) with generic imatinib when it becomes available in United States in 2016. In the year following generic entry, imatinib's price is expected to drop 70% to 90%. We hypothesized that initiating treatment with generic imatinib in these patients and then switching to the other tyrosine-kinase inhibitors (TKIs), dasatinib or nilotinib, because of intolerance or lack of effectiveness ("imatinib-first") would be cost-effective compared with the current standard of care: "physicians' choice" of initiating treatment with any one of the three TKIs.

Methods: We constructed Markov models to compare the five-year cost-effectiveness of imatinib-first vs physician's choice from a US commercial payer perspective, assuming 3% annual discounting ($US 2013). The models' clinical endpoint was five-year overall survival taken from a systematic review of clinical trial results. Per-person spending on incident CML-CP treatment overall care components was estimated using Truven's MarketScan claims data. The main outcome of the models was cost per quality-adjusted life-year (QALY). We interpreted outcomes based on a willingness-to-pay threshold of $100 000/QALY. A panel of European LeukemiaNet experts oversaw the study's conduct.

Results: Both strategies met the threshold. Imatinib-first ($277 401, 3.87 QALYs) offered patients a 0.10 decrement in QALYs at a savings of $88 343 over five years to payers compared with physician's choice ($365 744, 3.97 QALYs). The imatinib-first incremental cost-effectiveness ratio was approximately $883 730/QALY. The results were robust to multiple sensitivity analyses.

Conclusion: When imatinib loses patent protection and its price declines, its use will be the cost-effective initial treatment strategy for CML-CP.

Figure 1.

A simplified Markov diagram of generic imatinib-first vs physician’s choice (the current standard of care) treatment strategies for treating chronic myeloid leukemia in chronic phase. Under physician’s choice, patients have equal probability of beginning on imatinib, dasatinib, or nilotinib and remain on a drug until they reach a chance node. The chance nodes depicted in the figure represent CCyR at 12 months (or, as noted in the Methods, EMR at 3 months). Patients have three possible outcomes prior to reaching the first chance node, whether at 12 months in the first CCyR model or three months in the second EMR model: remaining on TKI therapy, progressing to AP/BC, or death. Patients who respond positively to a TKI stay on it the remainder of time, and overall survival since progression to AP/BC or death is uncommon after that point. Patients who fail their initial TKI because of intolerance or lack of efficacy can switch once (*) at 12 months (or 3 months in the EMR model) to another TKI. Under generic imatinib-first, 100% of patients begin on imatinib and only switch to nilotinib or dasatinib because of intolerance or if a CCyR (or EMR) was not reached. Some patients who fail under TKI therapy transition to the AP/BC state, which includes the risk of death. *Indicates where one switch at 12 months (or 3 months) can take place. AP/BC = accelerated phase/blast crisis; CCyR = complete cytogenetic response; EMR = early molecular response; M = Markov node; TKI = tyrosine kinase inhibitor.

Figure 2.

A Bayesian multivariable probabilistic sensitivity analysis found imatinib-first to be cost-effective compared with physician’s choice in 99.7% of 10 000 Monte Carlo simulations. The circular line indicates the 95% confidence interval of incremental cost-effectiveness ratios (ICERs) among simulations, and the dotted diagonal line indicates the willingness-to-pay threshold, which has a slope of $100 000/QALY. Simulations appearing below this line favor the imatinib-first strategy as cost-effective. Incremental effectiveness along the x-axis is measured in units of quality-adjusted life-years (QALYs). Incremental cost along the y-axis is measured in units of US dollars ($), adjusted for inflation to 2013. The ICER of each simulation is calculated as a ratio of incremental cost over incremental effectiveness ($/QALY).