Evolving Racial/Ethnic Disparities in AML Survival in the Novel Therapy Era: Real-World Evidence of Improved Survival in Older Patients with the Largest Improvement in Non-Hispanic Black Patients
Authors: Wang Xin , Gimotty Phyllis , Matthews Andrew H , Mamtani Ronac , Luger Selina M , Hexner Elizabeth O , Babushok Daria V , McCurdy Shannon R , Frey Noelle V. , Jordan Bruno Ximena , Porter David L. , Gill Saar , Martin Mary Ellen , Paralkar Vikram R , Maillard Ivan , Loren Alison W , Perl Alexander , Pratz Keith W , Getz Kelly D. , Lai Catherine 
Published: December 2023

Introduction: The approval of venetoclax (VEN)-based frontline therapy for acute myeloid leukemia (AML) in November 2018 marks a new era of AML care. Racial/ethnic disparities have been increasingly recognized in AML with historically inferior outcomes reported in non-Hispanic Black (NHB) patients relative to non-Hispanic White (NHW) patients. The advances of novel therapeutics offer an unprecedented opportunity to narrow the care gaps between patient groups; but they also create new challenges related to testing, clinical decision-making, and care coordination. Currently, little is known about the impact of race/ethnicity on the recent advances in AML management. We performed a retrospective analysis leveraging real-world data to examine the magnitude and mechanisms of racial/ethnic disparities in modern AML care.
Methods: Adult patients from Flatiron Health, a nationwide, electronic health record derived, de-identified database, with AML diagnosed between January 2014 to December 2018 (Pre era) and January 2019 to October 2022 (Post era) who identified as NHW, NHB or Hispanic and received at least one line of anti-leukemic therapy were included. Overall survival (OS) was defined from the time of therapy initiation to the time of death. Multivariable Cox regression models were used to compare the hazards of death for NHB and Hispanics relative to NHW. Predicted survival curves were then computed. Pre-planned sensitivity analyses including patients with 1) no ethnicity information, 2) no anti-leukemic therapy, and 3) care gap &gt;100 days from diagnosis to induction were performed.
Results: 2998 patients in Pre era (2566 NHW, 221 NHB, 211 Hispanics) and 2098 patients in Post era (1809 NHW, 162 NHB, 127 Hispanics) were included. Older patients with more comorbidities and worse disease biology (Table 1) were treated in Post era. After adjusting for race/ethnicity, age and Hematopoietic Cell Transplant Specific Comorbidity Index (HCT-CI), patients in Post era had a 10% decrease in the hazard of death compared to Pre era (HR 0.90, 95% CI 0.83-0.96). The difference was driven by OS benefits observed in patients aged &gt;70 years (HR 0.82, 95% CI 0.75-0.91).
NHB and Hispanics were younger at diagnosis than NHW in both eras. Lower socioeconomic status was observed in NHB and Hispanics. No difference in ELN2017 risk stratification was observed (Table 1). After adjusting for age and HCT-CI, NHB had a 22% increased hazard of death compared to NHW in Pre era (HR 1.22, 95% CI 1.04-1.43); whereas Hispanics had comparable outcomes (HR 1.01, 95% CI 0.84-1.21). Strikingly, the survival disparity between NHB and NHW in Pre era was not observed in Post era with predicted 2-yr OS rate being 45.3% and 39.9%, respectively (HR 0.86, 95% CI 0.69-1.08) (Figure 1). Predicted 2-yr OS rates improved for NHB patients in both ≤70 years (42.3% vs. 53.2%) and &gt;70 years group (13.6% vs. 37.0%). No significant change in OS was observed in Hispanics between Pre and Post era (Figure 1). Results of all sensitivity analyses were consistent with primary analyses.
Molecular testing at diagnosis significantly differed by eras across race/ethnicity groups (overall 66.4% vs. 82.9%, p&lt;0.001). In contrast, molecular testing occurred more frequently in NHB at relapse in Post era (45.6% vs. 65.4%, p=0.020). Despite being older, more NHW received allogeneic transplant than NHB in Pre era (25.8% vs. 18.6%, p=0.046). In Post era, NHW were more likely to receive VEN-based induction therapy (46.9%, 37.0%, 35.4% in NHW, NHB and Hispanic, respectively, p= 0.003). Among patients who were tested and qualified, no difference was observed in the use of gemtuzumab ozogamicin, CPX-351, FLT3 inhibitors or IDH1/2 inhibitors across race/ethnicity.
Conclusions: In this large, real-world dataset, we demonstrate OS improvements in the era of modern AML care, particularly among patients &gt;70 years though their outcomes remain inferior to younger patients. Intriguingly, the largest OS improvement was observed in NHB, where the OS disparity between NHB and NHW in Pre era appears to have been mitigated. Hispanics have not experienced similar OS improvement in modern AML care. Ongoing analyses are focused on examining the mechanisms of survival trends observed with focus on assessing the contribution(s) of patient-, disease biology- and treatment-related factors in order to identify potential targets for intervention.
• Dr. Kelly Getz and Dr. Catherine Lai contributed equally