Acute myeloid leukemia during the venetoclax era: Trends in survival across demographic and socioeconomic groups.

Abstract Background Acute myeloid leukemia (AML) has historically been associated with poor survival outcomes. In 2018, the FDA approved the combination of hypomethylating agents (HMA) with venetoclax (V) based on the VIALE-A trial for patients 75 years and older or who have comorbidities that preclude the use of intensive induction chemotherapy. Patients treated with this combination regimen showed increased overall survival (OS) compared to those treated with HMA monotherapy. Demographic variables and socioeconomic (SE) factors often differentially affect the efficacy and accessibility of new treatments. This study examines survival trends in AML before and after this new combination was approved, looking at differences in OS in different demographic and SE groups. Methods: This study utilized the Surveillance, Epidemiology, and End Results (SEER) database (17 registries) to extract patients with AML diagnosed between 2016-2021. Patients were stratified by demographic factors (race, marital status, age) and socioeconomic factors (urban-rural setting based on 2023 SEER Rural-Urban Continuum Code Definitions). 3-year OS was compared between two cohorts: patients diagnosed pre-HMAV (2016-2018) and those diagnosed post-HMAV (2019-2021), using Kaplan Meier analysis, log rank tests, and z-tests to assess differences across demographic and SE subgroups. Groups with n < 200 were excluded. Survival analysis was limited to 3-year OS due to SEER data availability through 2022. Results: A total of 12,243 patients diagnosed with AML between 2016-2021 were included. Of these, 4,947 patients were diagnosed between 2016-2018 (pre-HMAV) and 7,296 patients were diagnosed between 2019-2021 (post-HMAV). OS improved from 31.6% pre-HMAV to 34.7% post-HMAV (p<0.01). For racial groups in the pre-HMAV period, OS from highest to lowest was 40.9% for Hispanic, 33.4% for non-Hispanic (NH) Asian or Pacific Islander (API), 32% for NH black, and 28.7% for NH white patients (p<0.01). In the post-HMAV period, OS from highest to lowest was 42.6% for Hispanic, 36.4% for NH API, 32.9% for NH black and 31.79% for NH white patients (p<0.01). OS was significantly improved only for NH white patients over time (28.7% pre-HMAV vs 32.9% post-HMAV, p<0.01). For marital status, OS was 44.2%, 32.5%, 26%, and 10.1% for pre-HMAV (p<0.01) and 43.0%, 37.5%, 28.5%, 13.1% for post-HMAV (p<0.01) for patients who were single, married, divorced, and widowed, respectively. OS was improved only for married individuals over time (32.5% pre-HMAV vs 37.5% post-HMAV, p<0.01). Among age groups, as expected, the highest OS was observed for patients <25 years old pre- and post-HMAV (70.9% and 83.0%, p<0.01), and the lowest for patients >85 years old (3.0% and 4.7%, p<0.01). The <25-year-old, 65–74-year-old, and 75–84-year-old age groups had a significant difference in OS between pre-HMAV vs post-HMAV (70.9% vs 83.0%, 20.8% vs 26.3%, and 6.8% vs 12.4%, p<0.01). In urban-rural settings, no significant OS increase was observed pre- and post-HMAV. Counties in metropolitan areas with a population >1 million had the highest OS both pre- and post- HMAV (33.0% and 35.7%, p<0.01) while nonmetropolitan counties adjacent to a metropolitan area had the lowest OS pre- and post- HMAV (23.6% and 28.1%, p<0.01). Conclusions With regards to race, marital status, and age, this data suggests that certain racial groups (NH white), marital groups (married) and age groups (<25-, 65-74-, and 75–84-years-old) receive a greater benefit by advances in AML therapy. Further investigation into causes of this differential benefit among different groups is warranted. Furthermore, as there are significant differences in OS in various groups post-HMAV, it is imperative to further investigate causes of lower OS among groups with the lowest OS (ie patients who are NH white and black, widowed, 85+ years old, and who live in nonmetropolitan counties adjacent to a metropolitan area) to see if there is anything we can do as providers to help, such as providing additional social support for unmarried individuals and treatment modifications for older adults.