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Tuesday, December 13, 2022

Hispanic Patients With AML Have Distinct Genetic Makeup & Worse Outcomes

By Dibash Kumar Das, PhD

The Hispanic population is the largest minority group in the U.S., accounting for approximately 19 percent of the total population. The term Hispanic/Latino refers to people of Cuban, Puerto Rican, Mexican, South/Central American, or other Spanish-speaking cultures, regardless of race. Unfortunately, U.S. Hispanics experience many different health disparities, including cancer health disparities, resulting in poor survival outcomes and a reduced quality of life.

To better comprehend disparities in Hispanic patients with acute myeloid leukemia (AML), Guzman and colleagues characterized and compared clinical features, mutational landscape, and disease outcomes of AML patients from Mexico (Mex) and Hispanic AML patients living in U.S. (A-Hisp) and to non-Hispanic White (A-NHW) patients. The study was presented at the 2022 ASH Annual Meeting and Exposition (Abstract 4945).

The researchers investigated molecular features and outcomes of adult AML patients in four cohorts:

  • Cohort 1 (Mex): 48 AML patients diagnosed and treated with anthracycline and cytarabine combination (90%) at the Hospital General de Mexico.
  • Cohort 2 (A-Hisp, A-NHW): 48 adult AML patients who self-identified as Hispanic and 1,496 non-Hispanic White patients similarly treated as cohort 1 on frontline Alliance protocols.
  • Cohorts 3 & 4: Additional reported Hispanic cohorts in the U.S. and large international cohorts for validation of the identified molecular and clinical features.

Mutational status of 55 protein-coding genes in addition to the main fusion gene rearrangements at time of diagnosis were determined using targeted NGS platforms.

The findings revealed that median age at diagnosis for cohorts 1 and 2 was younger than reported for AML, 38 years old (15-86) for cohort 1 versus 45 years old (17-83) for cohort 2. Somatic mutations were detected at similar rates for Hispanic populations: 96 percent of patients in cohort 1 and 94 percent of A-Hisp patients in cohort 2. FLT3 was the most prevalent mutation among the cohorts: (Mex 29%, A-Hisp 33%, A-NHW 42%, p=0.654). Other prevalent mutations included: CEBPA (Mex 21%, A-Hisp 15%, A-NHW 13%, p=0.214), TET2 (Mex 19%, A-Hisp 8%, A-NHW 16%, p=0.322), DNMT3A (Mex 19%, A-Hisp 18%, A-NHW 24%,p=0.5498), RUNX1 (Mex 15%, A-Hisp 0%, A-NHW 12%, p<0.001), and NPM1 (Mex 12%, A-Hisp 29%, A-NHW 35%, P=0.002). Fusion genes were discovered in 21 percent of patients.

Although some commonalities were discovered in the genetic alterations between the two Hispanic cohorts, the median overall survival (OS) was worse for the Mexican cohort (9 months) compared to the OS for cohort 2 (A-Hisp 15mo, A-NHW 14mo). Strikingly, CEBPA-mutated AML was overrepresented in both cohort 1 and A-Hisp (cohort 2). The prevalence of mutated NPM1 was the most notable difference between the two Hispanic cohorts (Mex vs. A-Hisp); NPM1 was higher in the U.S. A-Hisp dataset, similar to what is described in other international cohorts for de novo AML. The molecular differences were validated in the two additional international cohorts.

Oncology Times connected with senior author, Monica L. Guzman, PhD, for additional insights into the study. She is Associate Professor of Pharmacology in the Department of Medicine at Weill Medical College of Cornell University.
 
Oncology Times: How can the findings of this study potentially improve clinical decision-making?
Guzman: “Identifying the molecular abnormalities in AML in Hispanic populations (ancestry-based, as opposed to self-reported) will provide significant insight into the differences and similarities that characterize AML in the Hispanic population compared with non-Hispanic White populations. Furthermore, if there are unique molecular features within Hispanic subgroups (based on ancestry), this could result in improved diagnostic assay development and eventually access to adequate treatments for Hispanic patients especially those in low-income countries. Furthermore, this will potentially lead to clinical trials designed and tailored to improve the treatment of AML in Hispanic populations."

Oncology Times: As indicated in the study, the root cause of these disparities is likely multifactorial. Are there any state or national programs that are working to improve the disparities in Hispanic patients with AML by promoting awareness, removing barriers to health care access, and ultimately improve health outcomes in this population?
Guzman: “Many groups are working on ways to remove barriers, including the American Society of Hematology; that is why we are so excited about this pilot study, to begin to understand what those barriers are. Comparing the biology and outcomes between Hispanic/Latinx patients in their home countries and Hispanic/Latinx patients living in the U.S. will enable us to unveil such barriers. We are currently extending our study to additional countries through collaborations, such as Bolivia, Colombia, and Brazil."

Oncology Times: What future research may be beneficial to determine other component causes of health disparities in outcomes among Hispanic patients with AML versus non-Hispanic White patients?
Guzman: “The next steps include looking into the role of certain inherited mutations and other predisposing factors that may affect clinical outcomes, in addition to other genetic factors that can affect specific drug responses."

Dibash Kumar Das is a contributing writer.​