Disparities in AML Survival in the Targeted Therapy Era: Real World Evidence of Enhanced Equity of Outcomes for Patients in Medically Underserved Areas
Authors: Tuz Zahra Fatima , Ong Faustine , Shahzad Moazzam , Chan Onyee , Al Ali Najla H. , Lancet Jeffrey E , Walker Alison R. , Sallman David , Komrokji Rami S. , Yun Seongseok , Kuykendall Andrew T. , Padron Eric , Xie Zhuoer 
Published: December 2024

Background and Significance
Survival outcomes of elderly patients with acute myeloid leukemia (AML) have improved since the approval of venetoclax (VEN) in combination with hypomethylating agents (HMAs). Federal medically underserved areas (MUAs) are geographically defined and have a lack of sufficient primary care providers, high infant mortality, a high percentage of the population below the poverty line, and/or a high percentage of the elderly population (age =/&gt;65 yrs.).
Novel therapies in AML present a promising opportunity to narrow the healthcare gaps for the underserved patients as these treatments have become accessible in the community. Unlike the traditional intensive induction chemotherapy, HMA+VEN can be administered outpatient. However, there are challenges related to laboratory monitoring, transfusion support, and care coordination with these therapies. Currently, there is very little understanding of the impact of recent advances in AML management on the outcomes of patients residing in locations with limited access to healthcare.
Aims
The purpose of this study was to compare the characteristics, survival outcomes, and treatment patterns of patients residing in the federally designated MUAs with those who are not residents of MUAs and who received frontline treatment with HMA+VEN for AML at our institution.
Methods
We conducted a retrospective review of our AML patient database. We selected the patients who were diagnosed with AML between November 2017 and June 2023 and received HMA+VEN as frontline therapy. We divided the patients into 2 groups (MUA vs non-MUA) based on the MUA status of their residential address. MUA status was determined by using the online tool from the Health Resources and Services Administration. Data was collected by chart review and analyzed for patient demographics, disease characteristics, and outcomes.
Results
A total of 247 patients were analyzed. MUA, n= 160 and non-MUA, n =87. The median age at diagnosis was 75.0 years (range: 27.8-92.6) in the MUA group and 74.9 (range: 41.0-89.6) years in the non-MUA group (p=0.99). There were 60.0% (96/160) males in the MUA group vs 56.3% (49/87) in non-MUA group (p=0.57). Comparative analysis of racial distribution between both groups did not show any statistically significant difference (p=0.26). Most patients in both groups identified as White, 91.3% (146/160) in the MUA and 89.7% (78/87) in the non-MUA group. Most patients had ECOG of 1, MUA= 87.4% (139/159) vs. non-MUA= 89.7% (78/87) with no difference in the ECOG status of patients between the two groups (p=0.23). Next Generation Sequencing panel was performed on &gt; 95% patients in both groups (p=0.89). Risk stratification according to ELN 2017 criteria could be performed on all 160 patients in the MUA group and 85 out of 87 patients in the non-MUA group. Most patients had adverse risk AML, MUA = 67.5% (108/160) and non-MUA=64.7% (55/85). No difference in distribution of patients in the favorable, intermediate, or adverse risk disease category was observed (p=0.48). Twenty patients (12.5%) in the MUA group and 10 patients (11.4%) in the non-MUA group received allogeneic hematopoietic stem cell transplant (AHSCT.) Among the AHSCT recipients in both groups, 90% of patients received transplant in first complete remission (p=0.72). Estimated median overall survival (OS) was 11.1 (95% CI: 8.9-15.3) months in the MUA group and 10.0 (95% CI: 7.2-13.8) months in the non-MUA group with no statistically significant survival difference between both groups (p=0.27). The 2-year OS rate was 29% (95% CI: 22-38%) in the MUA group and 17% (95% CI: 10%-30%) in the non-MUA group. 55 patients (34.3%) in the MUA group and 27 patients (31.0%) in the non-MUA group received at least one cycle of HMA+VEN therapy at our institution (p=0.59).
Conclusions
Our study highlights the role of frontline therapy with HMA+VEN in improved OS for AML patients regardless of their residence in MUAs. The study population did have access to a comprehensive academic cancer center despite their MUA status, a factor that could have contributed to comparable OS in the MUA group. Our dataset includes a small minority of non-White patients and does not capture the intersectionality of race and ethnicity within the MUA population sufficiently. More studies are needed to ascertain if novel therapies in AML can deliver equitable outcomes for historically disadvantaged racial/ethnic groups within underserved areas.