Disparities in Genetic Profiles, Risk Stratification and Outcomes in Adults with Acute Myeloid Leukemia Comparing Patients of Hispanic and Non-Hispanic Ethnicity in Central California

Abstract

Acute myeloid Leukemia (AML) is the most common type of acute leukemia in adults. Ethnic disparities due to distinct biology and socioeconomic status have been described in AML. Prior studies indicated Hispanic AML patients had a younger age at presentation, more frequent high-risk mutations, and worse survival compared with non-Hispanics. We conducted a retrospective study to investigate the differences in AML risk stratification, mutational profiles and outcomes between Hispanic and non-Hispanic AML patients treated at Community Medical Centers (CMC) in Central California. Methods: We retrospectively analyzed patients ≥ 18 years diagnosed with AML between January 2016-December 2022 and treated at CMC in Fresno, CA. Patients with Acute promyelocytic leukemia and patients without complete cytogenetic and molecular data were excluded. The clinical data including age, sex, ethnicity, race, zip code, WBC on diagnosis, cytogenetics, molecular data and treatment regimens were reviewed. Molecular profiling was performed by next generation sequencing using established myeloid panels by NeoGenomics (NeoTYPE comprising of 63 genes) or Foundation One Heme laboratory (406 genes). Risk groups were identified based on the European Leukemia Network (ELN) 2022 criteria. RedCap data collection tool was used for data collection. A comparison of patient characteristics and rate of genetic alterations between Hispanic and Non-Hispanic patients was done using the Fisher exact test or Chi-square test. Kaplan-Meier Curve with log-rank test was used for evaluation of overall survival (OS) and progression-free survival (PFS). Results: 201 patients met the study criteria, 30 of them did not receive treatment and were included for their diagnostic data only but excluded from the survival analysis. The mean age at diagnosis was 65.6. 58.5% were males and 30% were Hispanic. Hispanic patients were younger than non-Hispanics (57.6 vs 64.6 years, p=0.01). Hispanic patients were also more likely to live in the relatively low Socioeconomic status (SES) neighborhoods (i.e., living in zip codes with the 1st or 2nd quartile of median income level) p=0. 007. More Hispanic patients needed interpreter P<0.001. However, Hispanics were more likely to experience favorable risk AML (8.4 % vs 0.7%, p=0.012), while non-Hispanics had higher rate of poor risk disease (63.8 Vs 55.9%, p=0.012).). There was no significant difference between Hispanics and non-Hispanics in terms of sex, de novo versus secondary AML, WBC at time of diagnosis, Extramedullary or Central nervous system (CNS) involvement, type of induction regimen or rate of consolidative or subsequent allogeneic stem cell transplant. Median OS in Hispanics was 17.3 months compared to 10.28 months for non-Hispanics, p=0.117.and median PFS for Hispanics was 9.17months compared to non-Hispanics at 6.04 months P=0.034 (Figure 1). In univariate analysis PFS and OS were better in patients with normal cytogenetics compared to those with abnormal cytogenetics (15.3 vs 3.52 months and 20.4 vs 7.69 months respectively, p < 0.001) and in patients with favorable compared to intermediate risk and poor risk groups (84.5 vs 11.4 vs 4.1 months for PFS and Non reached vs 18.1 vs 7.8 months for OS, p< 0.001). There was no significant effect of income level in terms of OS or PFS. The most common genetic mutations in our patients were NPM1, FLT3-ITD, DNMT3A, TET2 and TP53. However, there were differences in the rates between Hispanics and non-Hispanics. 5q deletion and STAG2 were more common in non-Hispanics while KMT2C was detected more in Hispanics (table 1). Conclusion: Our study identified biologic differences between Hispanic and non-Hispanic AML patients with heterogeneity in genetic mutations. While Hispanic patients had lower income, they were younger at diagnosis and more likely to have favorable risk AML. Hispanic patients had better PFS and a trend towards improvement in OS. Further studies on larger patient population are warranted to evaluate the effect of ethnicity and SES on outcomes of AML patients.