Inequalities in Treatment Utilization Among Older Medicare Beneficiaries with Newly Diagnosed Acute Myeloid Leukemia Who Are Ineligible for Induction Therapy
Authors: Zeidan Amer M. , Xu Yanqing , Kapustyan Tatyana A. , Miu Kaylee , Chen Cheng , Kamalakar Rajesh , Lin Chia-Wei , Ma Esprit , Montez Melissa , Wu Zheng , Yee Tracy , Sun Haiyan , Rava Andrew , Kim Sonia , Huntington Scott F 
Published: December 2024

Background:
For older adults with newly diagnosed acute myeloid leukemia (ND AML) who are ineligible for induction therapy, venetoclax (VEN) in combination with hypomethylating agents (VEN-HMAs) has replaced low-dose chemotherapy (cytarabine) or HMA monotherapy (HMA MONO) as the standard of care based on the Phase 3 VIALE-A trial (NCT02993523) results. While prior work identified ethnic and racial inequalities in in-hospital survival rates among AML patients in the US (Alam et al, 2023), evidence of inequalities in AML therapy uptake among Medicare beneficiaries is limited. This study examined AML therapy receipt, differences in sociodemographic characteristics among ND AML Medicare patients, and temporal trends in first-line (1L) AML therapy utilization.
Methods:
This retrospective cohort study used 100% Medicare fee-for-service data from 2016-2022 to identify beneficiaries with ND AML predicted to be ineligible for intensive therapy (ie, ≥1 inpatient or ≥2 outpatient AML claims and were aged 75+ or with comorbidities who were unfit for intensive treatment per the Ferrara criteria). Patients diagnosed post-2019 (VEN era) were assessed for 1L treatment utilization and time-to-treatment initiation. The index date was the first AML diagnosis date. Patients were required to have ≥12 months of continuous Medicare Part A, B, and D enrollment preindex and ≥60 days postindex. Patients who had prior AML diagnosis, hematopoietic stem cell transplant, other malignancy, or prior AML therapy claims were excluded. Treated patients received active AML 1L therapy (HMAs, VEN or other targeted therapies, chemotherapy) within 60 days after diagnosis. Untreated patients had no active AML therapy postdiagnosis (patients may have had supportive therapy). Logistic regression was applied to generate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) to quantify associations between patient characteristics and receipt of AML therapy. The model adjusted for age, Charlson Comorbidity Index (CCI), postindex follow-up time, sex, race, region, rural/urban, select comorbidities, and diagnosis year. Descriptive analysis assessed 1L treatment uptake, and time-to-event outcomes were analyzed using Kaplan-Meier methods.
Results:
A total of 5647 treated and 6507 untreated individuals with ND AML were included in the study. Following logistic regression analysis, a 1 year increase in age (OR = 0.94, 95% CI: 0.94, 0.95), and female sex (OR = 0.71, 95% CI: 0.65, 0.76) was associated with lower odds of receiving AML treatment within 60 days of diagnosis. No statistically significant differences were detected between people of color vs White (OR = 0.96, 95% CI: 0.83, 1.10) or patients residing in rural and urban areas (OR = 0.94, 95% CI: 0.86, 1.04). Higher CCI scores were associated with lower odds of receiving AML treatment (OR = 0.90, 95% CI: 0.88, 0.92). Patients diagnosed in the earlier years of the study (2017/2018) were also less likely to receive any AML treatment (OR = 0.65, 95% CI: 0.60, 0.70) compared with those diagnosed in later years (2019+).
Among 3864 patients who were diagnosed during the VEN era (2019+), 67.3% of patients received VEN-based treatment (including 41.1% who received VEN-HMA), 18.9% received HMA MONO, and 5.4% received other targeted therapies. Specifically for targeted therapies, 1.1% received ivosidenib, 1.1% received gilteritinib, 2.3% received midostaurin, and 1.7% received enasidenib. In 2019-2022, the usage of VEN-based treatment increased (2019: 56.7%, 2022: 77.4%), while HMA MONO uptake decreased over time (2019: 27.7%, 2022: 10.8%). Time to treatment initiation was significantly shorter for VEN-HMA compared to other targeted therapies (0.39 vs 0.59 months; p &lt;0.0001).
Conclusion:
AML therapy uptake was significantly less likely among female patients, older patients, and those diagnosed in earlier years (pre-2019), after adjusting for confounders. Patients diagnosed in later years (2019+) were more likely to receive AML treatment and 67.3% received VEN-based treatment. Those initiating VEN-HMA also had shorter time to treatment initiation. Because our analysis was based on claims data, clinical performance status, lifestyle factors, disease severity, and geographical differences were not fully captured. Further evaluations are warranted to identify opportunities for optimizing care, especially for elderly female patients with ND AML and comorbidities.