100 Years of Chronic Myeloid Leukemia Prevalence in France
Authors: Delord Marc 
Published: October 2019

Abstract
Purpose: Imatinib and other rationally designed tyrosine kinase inhibitors (TKI) has dramatically changes the fate of chronic myeloid leukemia (CML) patients. Almost always fatal a few years ago, CML is now associated to a near-normal life expectancy for a majority of patients, provided a lifelong adherence to TKI-based treatment. This situation where CML can be regarded as a chronic disease have had mechanical consequences on the disease prevalence and overall costs supported by health care systems. We present here a fully detailed and comprehensive analysis of the French CML prevalence from 1960 to 2060.
Methods: We use the cohort component methodology to evaluate the CML prevalence from French population projection and different hypothesis on age- and sex-specific incidence rate, and relative survival of CML patients. Figure 1 gives an illustration of intermediate results at different time points.
Results: The CML prevalence in France, expressed in cases per 100,000 inhabitants, was estimated to be around 3 from 1960 to the 80's, 6 before the 2002, 17 in 2016, 25 in 2030 where the tendency inflects, and 30 after 2040. Considering the 100% relative survival hypothesis, a target CML prevalence were defined, the level of which will be nearly reached by 2060. Based on an annual cost of 40000 euros per patient, the cost per 100,000 inhabitants-year is then estimated to be around 700,000 euros.
Figure 2 summarize results: the blue line represents the estimated CML prevalence for France. It corresponds to 10 years relative survival hypothesis as reported in the literature for the different periods and our hypothesis for the future: 5% before the 70's, 10% by the late 80's, 35% before imatinib introduction, 47% in 2002 , 80% in 2006, 84% in 2016 and 90% in 2060. The black line corresponds to the 100% relative survival hypothesis. It is the target CML prevalence, that is, the prevalence of CML if the disease have had no impact on the relative survival of affected people. Green line corresponds in relative survival observed before imatinib use and the gray line corresponds to levels of relative survival observed in the 70's. These different estimates clearly show that not only the increase in CML prevalence is attributable to the use of TKI soon after 2002 but also to populations aging as illustrated by the target CML prevalence line.
Conclusion: Due to high rates in relative survival observed in CML patients after introduction of imatinib, the trajectory of the CML prevalence in France, as in other western countries, has changed. Given particular hypothesis on CML incidence rates, this trajectory will bring the CML prevalence to levels fully determined by population aging by the mid century, that is, when the proportion of the population aged 60 or more will stabilized in western countries. For France, we have estimated this level above 30 cases per 100,000 inhabitant.
Figure 1 Estimated number of CML patients by single age and sex, corresponding legal or projected population (and period specific relative survival hypothesis) in france in 1970 (A), 1980 (B), 2000 (C), 2010 (D), 2020 (E) and 2040 (F). Figure 1. Estimated number of CML patients by single age and sex, corresponding legal or projected population (and period specific relative survival hypothesis) in france in 1970 (A), 1980 (B), 2000 (C), 2010 (D), 2020 (E) and 2040 (F). Figure 2 CML prevalence estimate in France from 1970 to 2060 (see text). Figure 2. CML prevalence estimate in France from 1970 to 2060 (see text).

Disclosures
No relevant conflicts of interest to declare.