¹Universität Münster, Institut für Biometrie und Klinische Forschung, Münster, Germany
²Universität Bremen, Bremen, Germany

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Background: The analysis of trends in overall survival after leukemia is an ongoing research field [1], [2], [3], [4]. We characterized the improvement in overall survival after acute myeloid leukemia (AML) over 46 years based on US registry data.

Methods: We accessed unique patient data covering the years 1975 to 2021 from the US Surveillance, Epidemiology, and End Results Program (SEER) [5], [6]. Overall survival (OS) was analyzed by Kaplan-Meier estimates and Cox-proportional-hazard models [7] showing hazard ratios (HR_OS) per diagnosis year (reference 1975) by age (≤60 vs. 60+ years(y)), sex, and chemotherapy treatment (yes vs. no/unknown). An interaction term between cofactor and diagnosis year estimated group specific HRs for each year. A competing risk analysis (CRA) was performed with the Fine-Gray model [8], considering two competing events: “AML-related death” and “non-AML causes of death”. The CRA facilitated also an interaction-term to estimate sub-distribution HRs for the competing events (HR^AML and HR^other) by covariables.

Data was extracted using the SEER*Stat software [8]. Further data preparation and data analysis was performed within SAS software (Version 9.4 for Windows, SAS Institute Inc., Cary, NC, USA).

Results: From the current SEER data (4,633,916 oncologic cases) information of 37,615 unique patients (excluding patients under 18y or with missing survival times) were extracted and analyzed. 45.5% of patients were female, and the median age was 68y (range: 18-90y). 5-year OS rates improved monotonously over time (1975-1979: 4.5%, 2010-2019: 20.8%, p<0.0001). In the CRA we could attribute this trend to the AML-related mortality (HR^AML). HR^other showed no progress, also with respect to all analyzed covariables. Patients ≤60y displayed an overall improvement in HR^AML (HR^AML;1976: 1.186 (95%CI: 0.977, 1.441); HR^AML;2021: 0.276 (95%CI: 0.203, 0.375)). Older patients (60y+) had no benefit until the mid-2000s, thereafter a noticeable decrease in HR^AML can be found, i.e. HR^AML;2011 being the first showing a significant effect (HR: 0.790 (95%CI: 0.687, 0.908)). Treated patients showed a continuous reduction in risk (HR^AML;1976: 1.083 (95% CI: 0.934, 1.257) to HR^AML;2021: 0.384 (95%CI :0.327, 0.452)). Untreated patients displayed no such trends in HR^AML.

Conclusions & discussion: We hypothesize that the improved HR^OS in AML patients as well as the more specifically characterized improvement of HR^AML can be attributed to advancements in therapy specificity and efficiency [9]. The substantial change in HR^AML trend for older patients (60y+) in the mid-2000s could be related to a changing treatment paradigm in this cohort [10], [11], [12]. Our approach has several limitations, including insufficient information on patient characteristics, as well as a potential time-dependence in the age and chemotherapy covariates. These issues should be tackled in future research.

The authors declare that they have no competing interests.

The authors declare that an ethics committee vote is not required.

The contribution has already been published: [13]

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