A Temporal and Multinational Assessment of Acute Myeloid Leukemia (AML) Cancer Incidence, Survival, and Disease Burden
Authors: Anderson Laura J. , Girguis Mariam S. , Kim Ju-Hyeun , Shewale Jitesh B. , Braunlin Megan , Werther Winifred , Hidalgo-Lopez Juliana E. , Zaman Faraz , Kim Christopher 
Published: November 2021

Abstract
Introduction: As US and global populations continue to age, a corresponding rise in incidence of age-associated cancers including acute myeloid leukemia (AML) remains persistent (Kraywinkel & Spix, 2017; Reedijk et al., 2019; Siegel, Miller, & Jemal, 2020; Yi et al., 2020). Characterizing the current and future epidemiologic impact of AML is critical for assessing therapeutic demand and informing allocation of health care resources. However, very few recent publications have reported international estimates of AML diagnoses and none have projected future cases. In this study, we estimate current and future incidence of AML (2021-2040) in 29 countries from 4 continents. Next, we describe survival trends in the US over the last 4 decades and by age at diagnosis. Finally, we assess the societal burden of AML in 29 countries by calculating average years of life lost (AYLL) due to AML-related death in 2021.
Methods: Incidence rates were age-standardized to the World Health Organization (WHO) New World Population. For these calculations, age-specific rates were estimated using data from the International Agency for Research on Cancer's (IARC's) Cancer Incidence in Five Continents Volume XI (CI5-XI) database for 28 countries outside of the US (11 in Asia, 9 in Europe, 6 in the Americas, and 2 in Oceania). For US rates, data from National Cancer Institute's (NCI's) Surveillance, Epidemiology, and End Results (SEER) 21 were assessed. To project crude (unstandardized) incidence rates and the number of incident cases forward to 2040, age- and sex-specific incidence rates were applied to each country's age- and sex-specific population projections using data from the United Nation's World Population Prospects. Five-year Kaplan-Meier survival curves reflecting observed survival by year of diagnosis and age at diagnosis were derived using SEER 9 and SEER 18 databases, respectively. AYLL calculations utilized US age- and sex-specific mortality rates from the National Center for Healthcare Statistics (NCHS); non-US mortality rates were estimated by applying the incidence to mortality ratio from the US. The WHO's Global Health Observatory provided life expectancy data to estimate AYLL for each of the 29 countries.
Results: Age-standardized incidence rates ranged from 0.70 cases per 100,000 persons (Costa Rica) to 3.23 cases per 100,000 persons (United States) with a median of 2.28 cases per 100,000 persons (interquartile range (IQR): 1.61-2.71). Projected growth in incident AML cases varied from +3% (Russia) to +51% (Colombia) over the next 20 years; median growth in incident AML cases was +32% (IQR: 27%-43%). AML survival after diagnosis more than doubled in the US over the last 40 years with the following median survival times observed: 4 months (1978-1987) vs. 11 months (2008-2017). Five-year survival in the US was likewise extended during this period: 8% (1978-1987) to 28% (2008-2017). Disparate survival was observed when patients were stratified by age. During the period 2008 to 2017, US cases diagnosed 60 years and older (which represented 67% of all new AML cases) had a median survival of 3 months with a five-year observed survival (OS) of 10%; this was far lower than their younger counterparts (&lt; 60 years) who experienced a median survival of 60 months and a 5-year OS of 51%. The multinational assessment of societal disease burden due to premature AML death estimated a median AYLL of 19.6 years (IQR: 17.3-23.3 years).
Conclusion: This epidemiologic assessment of AML disease burden projected significant growth in new AML diagnoses over the next 20 years. In fact, we estimated the growth of AML cases to outpace population growth in most countries - a phenomenon that can be attributed in part to the disproportionate increase in the elderly population where AML is most persistent. Our analysis additionally confirmed differences in survival by age with younger patients exhibiting more favorable survival compared to older adults. This stark contrast in prognosis may be partly explained by the current treatment approach using stem cell transplant for younger, fit patients and the limited therapeutic options among older patients. Despite the noted improvements in survival over the last 4 decades, median survival among all AML patients remains poor highlighting the unmet medical need for novel therapeutic approaches.
Figure 1 Figure 1.

Disclosures
Anderson: Amgen: Current Employment, Current equity holder in publicly-traded company. Girguis: Amgen: Current Employment, Current equity holder in publicly-traded company. Kim: Amgen: Current Employment, Current equity holder in publicly-traded company. Shewale: Amgen: Current Employment, Current equity holder in publicly-traded company. Braunlin: Amgen: Current Employment, Current equity holder in publicly-traded company. Werther: Amgen: Current Employment, Current equity holder in publicly-traded company. Hidalgo-Lopez: Amgen Inc.: Current Employment, Current holder of stock options in a privately-held company. Zaman: Amgen: Current Employment, Current equity holder in publicly-traded company. Kim: Amgen: Current Employment, Current equity holder in publicly-traded company.