Treatment Patterns and Survival Outcomes for Very Elderly Patients with Acute Myeloid Leukemia: A National Cancer Database Study

Introduction: Most patients diagnosed with acute myeloid leukemia (AML) are 65 years and older, with many 80 years and older. Very elderly patients 80 years and older have increased incidence of adverse risk and high-risk genomic lesions. They are often not candidates for curative-intent therapies such as stem cell transplant but may be eligible for targeted therapeutics. Few studies have focused on this patient population, and this study seeks to analyze treatment patterns and survival outcomes of very elderly patients with AML.

Methods: The National Cancer Database was used to analyze patients 80 years and older diagnosed with AML between 2004 and 2021. Survival was estimated using the Kaplan-Meier method and compared across sociodemographic variables, diagnosis year, and available treatment data. Log-rank p-values were calculated, and chi-squared tests were used to compare the use of chemotherapy over time and across treatment facility types.

Results: This study included 31,195 patients. Median overall survival (mOS) was 1.71 months (mo) (95% confidence interval [CI]: 1.68-1.74). The mOS was longer in males compared to females (1.84 mo, 95% CI: 1.77-1.90 vs. 1.61 mo, 95% CI: 1.54-1.64; p < 0.01) and in patients 80-84 years old compared to those 85 years and older (2.17 mo, 95% CI: 2.07-2.23 vs. 1.31 mo, 95% CI: 1.28-1.38; p < 0.01). Asian patients had longer mOS compared to Black and non-Hispanic White patients (2.40 mo, 95% CI: 2.00-3.06 vs. 1.84 mo, 95% CI: 1.64-2.00 and 1.68 mo, 95% CI: 1.64-1.78, respectively; p < 0.01). Medicaid-insured patients had longer mOS compared to uninsured patients, those with private insurance, and Medicare patients (2.14 mo, 95% CI: 1.71–2.83 vs. 1.38 mo, 95% CI: 0.99-2.04; 1.68 mo, 95% CI: 1.51-1.81; and 1.71 mo, 95% CI: 1.64-1.74, respectively; p < 0.01).

Forty-six percent of patients received chemotherapy; 29% received multi-agent and 66% single-agent regimens. Twelve patients underwent bone marrow transplant and had a mOS of 15.57 mo (95% CI: 9.69-N/A). The mOS for those treated with multi-agent chemotherapy (MAC) was 5.95 mo (95% CI: 5.52-6.34) compared to 3.38 mo (95% CI: 3.22-3.52; p < 0.01) fore patients treated with single-agent chemotherapy. Patients treated at academic/research centers had longer mOS compared to those treated in community programs (2.33 mo, 95% CI: 2.23-2.43 vs. 1.48 mo, 95% CI: 1.41-1.54; p < 0.01).

Men received chemotherapy more often than women (50% vs. 42%, p < 0.05) and received MAC more often (32% vs. 29%, p < 0.01). Compared to those treated in the community, patients treated at academic centers more often received chemotherapy (59% vs. 39%, p < 0.01) and more often MAC (36% vs. 26%, p < 0.01). Patients aged 80-84 years were treated more often at an academic center (35% vs. 29%, p < 0.01) and with MAC (34% vs. 25%, p < 0.01) compared to patients 85 years and older.

Median OS improved significantly from 1.38 mo (95% CI: 1.31-1.45) in 2004-2008 to 1.68 mo (95% CI: 1.61-1.74) in 2009-2013, 1.87 mo (95% CI: 1.77-1.97) in 2014-2018, and 2.00 mo (95% CI: 1.87-2.14, p < 0.01) in 2019-2021. For patients receiving MAC, mOS increased from 3.75 mo (95% CI: 3.12-4.44) in 2004-2008 to 4.28 mo (95% CI: 3.61-5.19) in 2009-2013, 7.06 mo (95% CI: 6.28-8.02) in 2014-2018, and 7.66 mo (95% CI: 6.97-8.54) in 2019-2021. This increase was statistically significant between groups except between 2014-2018 and 2019-2021. The proportion of patients receiving chemotherapy increased from 35% in 2004-2008 to 44% in 2009-2013, 49% in 2014-2018, and 56% in 2019-2021 (p < 0.01), while use MAC decreased from 26% in 2004-2008 to 19% in 2009-2013 and 2014-2018 before rising again to 53% in 2019-2021 (p < 0.01).

Discussion: Despite improvements in mOS, prognosis remains poor for very elderly patients with AML, reflecting a major unmet need. The increase in single-agent chemotherapy use in 2004-2008 may reflect off-label use of hypomethylating agents (HMA) in this population. Significant gains in mOS were noted with MAC, and its use increased in 2019-2021, possibly due to approval of targeted therapies like venetoclax. Future work will focus on understanding complex treatment decisions for very elderly patients and the effect of novel multi-agent regimens such as HMA and venetoclax on treatment patterns and survival.