Improvement of Relative Survival in Elderly Patients with Acute Myeloid Leukemia Emerging from Population-Based Cancer Registries in Switzerland from 2001-2013
Authors: Schnegg-Kaufmann Annatina , Feller Anita , Boldomero Helen , Rovó Alicia , Manz Markus G , Gregor Michael , Efthymiou Anna , Bargetzi Mario , Hess Urs , Spertini Olivier , Chalandon Yves , Passweg Jakob R. , Stuessi Georg , Arndt Volker , Bonadies Nicolas 
Published: April 2021

Abstract
Introduction: Acute Myeloid Leukaemia (AML) is a rare disease with increasing frequency in the elderly and an emerging impact on health care resources. Trends of classification, incidence, mortality, and survival of AML patients have not yet been reported for Switzerland. Given the demographic ageing, we were mainly interested to investigate whether elderly patients have benefited on a population-based level from the recent changes in AML management.
Methods: We performed a population-based, observational analysis of AML cases reported to Cantonal Cancer Registries in Switzerland. Data was aggregated by the National Institute for Epidemiology and Cancer Registration and stratified for the two time-periods 2001-2007/2008-2013. The Swiss Federal Statistics Office provided canton-specific mid-year estimates of the size of the general population and mortality statistics. Data from transplanted patients was provided from the registry of the Swiss Blood Stem Cell Transplant Group .
Results: 2'351 new AML cases were registered within the observation time at a median age of 68/67 yrs (range 0-96 yrs). The extrapolated mean annual frequency increased from 275 to 305 AML cases (+10.8%) in the two time periods. In contrast, the age-standardized incidence and mortality rates remained stable (3.0 [95 CI: 2.8-3.2] and 1.9-2.0 [1.8-2.1] per 100'000 person-years, respectively). Incidence was up to 1.4-fold more frequent in males and increased up to 7 fold in patients &gt;75 yrs of age. The fraction of non-classifiable AML cases decreased over time (54.6%/41.8%), but remained high in elderly patients (75-84 yrs: 54.1%, 85+ yrs: 59.1%). As expected, 5-year relative survival (RS) correlated directly with AML risk classes (favorable: 61.7-68.4%, intermediate: 14.9%-27.3%, adverse: 11.4%-20.4%, non-classifiable: 11.4%-14.7%) and inversely with age (&lt;65 yrs: 42.6-42.7%, 65-74 yrs: 5.2%-13.5%, 75-84 yrs: 2-3%; 85+ yrs: 0%). RS improved only modestly in all age classes over time (19.2%/23.3%). Most interestingly, a trend towards improved RS was found in AML patients aged 65-74 yrs (5.2%/13.5%) and with intermediate (20.4%/27.3%) as well as adverse risk (11.4%/ 21.9%). This trend was multifactorial and only partially explained by an increased referral to allogeneic HSCT (1.4%/7%) or inclusion in clinical trials of patients ≥65 yrs.
Conclusions: AML incidence remained stable during the observation period, indicating that the 10.8% raise in annual case-frequency is mainly related to population growth and ageing and not to an increase of age-specific risk. AML classification improved over time, but non-classifiable AML cases remained high in elderly patients, suggesting that diagnostics and reporting is less accurate with increasing age. A trend towards improved RS was found in AML patients aged 65-74 yrs and with intermediate as well as adverse risk. These trends were caused by multiple factors and mainly based on the general changes of treatment management of AML patients ≥65 yrs. Survival of elderly AML patients remains dismal. Nevertheless, recent progress in clinical management of elderly AML patients resulted in an emerging improvement of survival on a population-based level in Switzerland. The demographic trend will further increase AML burden and has to be taken into account for structural as well as financial considerations for future health care systems.

Disclosures
Gregor: AbbVie: Other: Personal Fees; Celgene: Other: Personal Fees, Non-Financial Support; Gilead: Other: Personal Fees; GlaxoSmithKline: Other: Personal Fees; Janssen: Other: Personal Fees, Non-Financial Support; Mundipharma: Other: Personal Fees; Novartis: Other: Personal Fees, Non-Financial Support; Roche: Other: Personal Fees, Non-Financial Support.