Access to Novel Therapies Impacts Overall Survival (OS) in Low Socioeconomic (SES) Acute Myeloid Leukemia (AML) Patients (Pts)

Introduction: AML is a highly morbid condition with a 5-year OS rate of 30.5%. However, advancements in treatment options have improved OS (Ho 2023). We previously reported lower SES was associated with worse OS in AML pts (Duarte 2023). This analysis expands on previous research to further describe the OS difference in this population.

Methods: This study used the nationwide Flatiron Health electronic health record derived de-identified database with a data cutoff date of June 30, 2022. Pts were over 18 years old with a diagnosis of AML. Pts with acute promyelocytic leukemia or therapy related AML were excluded. The primary outcome was OS defined as time between date of diagnosis and date of death or last follow up stratified by demographic factors of race, ethnicity, sex, and SES. Area-level SES is an index quintile based on an area-level measure providing insight into pts’ neighborhood SES conditions with a score of 1 representing the lowest SES and 5 representing the highest (Guadamuz 2022).

Results: 3333 pts were included in the analysis. 59.9% of pts were 65 or older, 58.2% were male, 75.2% were White, and 93.4% were non-Hispanic. SES breakdowns were as follows: SES 1 14.6%, SES 2 18.4%, SES 3 22.3%, SES 4 24.9% and SES 5 19.8%.

With a median follow up of 3.3 years, the median OS for the population was 15.8 months (mos) (95% CI 15, 16.9). Median OS by SES was longer for pts with SES status 4 or 5 (SES high) at 17.2mos (95% CI 15.7, 18.6) compared to pts with SES 1 or 2 (SES low) at 16.1mos (95% CI 14, 18) (p = 0.03). Looking at pts over age 60, the difference in OS by SES was maintained with high SES OS at 13.3 mos (95% CI 12.1, 14.5) and low SES OS at 10.8 mos (95% CI 9.4, 12) (p =0.0009).

To elucidate the etiology of OS difference, further analysis was done. Given FDA approval of multiple novel agents for AML in 2017 and 2018, OS was examined by diagnosis before and after 2017. There was no significant difference in OS for pts diagnosed before or after 2017 (16.5mos versus 15.7mos respectively, p = 0.12). Pre-2017 OS for low versus high SES was not significantly different (17.2 mos versus 18.2 mos respectively, p = 0.35). However, when OS was examined post-2017, pts with high SES had an OS of 17 mos (95% CI 15.3, 18.4) while low SES had OS of 15.2 mos (95% CI 13.2, 17.7) (p=0.039).

We then examined first line treatment pre- and post-2017. Pre-2017 treatment for low and high SES pts respectively was 7+3 (52.1%/48.7%), single agent azacitidine (aza) or decitabine (29.9%/28.5%), lose dose cytarabine (5.3%/3.6%), clinical trial (4.9%/11%), FLAG-IDA (4.3%/6.9%) or other treatment (3.4%/1.3%). There was a statistically significant difference between low and high SES pts (p = 0.0081).

Post-2017 treatments for low and high SES pts respectively was 7+3 (43.4%/35.7%), clinical trial (5.2%/8.2%), FLAG-IDA (4.3%/4.4%), lose dose cytarabine (3.4%/ 3.5%), novel AML agent (0.4%/1.1%), other (2.4% vs 2.5%) single agent aza/decitabine (17.3% vs 17.5%) or venetoclax (ven) plus aza or decitabine (23.6 vs 27.1%). The differences were statistically significant (p = 0.0277). In the era of novel therapies low SES pts were more likely to receive induction chemotherapy at a greater rate than high SES pts. Additionally, they received ven and aza or decitabine at a lower rate than high SES pts.

Discussion: This is an updated analysis of AML pts from academic and community centers. Prior studies have demonstrated the impact of SES on OS in AML pts. This analysis demonstrates worse OS in pts low SES compared to those with high SES after 2017. This timepoint is important in AML therapy as prior to 2017 there were limited options for treatment; post 2017 there was a significant increase in FDA approved therapeutic options including ven.

While novel combinations such as hypomethylating agents with ven have revolutionized care for elderly pts ineligible for intensive chemotherapy, they come at a cost. The estimated cost of ven is over $100,000 per year (Vaughan 2019). While most pts included in this analysis would meet criteria for Medicare given their age, it is well established that pts with lower SES often face barriers to medication access due to the Medicare Part D coverage gap (Zissimopoulos 2015).

This analysis demonstrates that low SES AML pts may be experiencing decreased OS due to a lack of access to novel agents such as ven or decreased enrollment in clinical trials. Further investigation into disparities in insurance coverage will be necessary to further policy change to decrease costs for pts.