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Study Finds Survival Disparities and Mutational Differences for Black Patients Younger Than 60 With AML


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It has been well documented that, collectively, Black individuals have the highest death rates and shortest survival of any racial/ethnic group in the United States for most cancers. Black men also have the highest cancer incidence.1 Although the causes of these inequities are complex and include social and economic disparities, as well as inaccessibility to quality health care, differences in the biology of cancer in Black patients may also be playing a role in survival outcome.

Bhavana Bhatnagar, DO, of The Ohio State University Comprehensive Cancer Center, Columbus, and colleagues investigated the outcomes of adults with acute myeloid leukemia (AML) and characterized molecular features of the leukemia cells in Black patients compared with White patients. After accounting for other variables, they found that self-reported Black race was independently associated with poor survival of patients younger than age 60 diagnosed with AML. There is an urgent need to address this survival disparity in younger Black patients, as well as to conduct larger studies to establish molecular risk profiles of these patients, according to the study authors.2,3 The study findings were presented virtually at the Plenary Scientific Session of the 2020 American Society of Hematology (ASH) Annual Meeting & Exposition and published concurrently in Cancer Discovery.


Survival analyses in Alliance patients identify Black race as an independent poor survival prognosticator in patients with AML besides established molecular markers.
— Bhavana Bhatnagar, DO, and colleagues

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Study Methodology

The researchers first examined survival outcomes and socioeconomic characteristics of 25,523 adults diagnosed with AML, excluding acute promyelocytic leukemia, between 1986 and 2015 as identified by the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. To characterize molecular features, the researchers performed targeted sequencing on 81 genes in 1,339 patients treated on front-line Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology protocols based on standard-intensity cytarabine/anthracycline induction followed by consolidation therapy between 1986 and 2015. No Alliance patient received an allogeneic stem cell transplant in the first complete remission.

Study Results

The researchers found that although survival of patients with AML as a whole has improved across 3 decades in the SEER registry, the survival disparities between Black and White patients with AML have actually widened over time, despite improved treatment and understanding of the disease. From a socioeconomic standpoint, they found that young Black patients, specifically, more often resided in metropolitan areas, and a higher percentage of younger Black patients with AML came from households with an income below the poverty level. After other variables in the multivariable model were accounted for, Black race was found to be independently associated with worse survival outcomes. Specifically, younger Black patients had a higher risk of death compared with White patients (hazard ratio [HR] = 1.27), with a 3-year overall survival rate of 34% vs 43%, respectively (P < .001).

To evaluate whether this survival disparity also persisted for younger Black patients with AML treated in the setting of clinical trials, the researchers analyzed the survival of patients similarly treated on Alliance protocols. Although there was no difference in complete remission rates between Black and White Alliance patients, young Black patients had inferior disease-free survival (median, 0.8 years vs 1.4 years, P = .02) and overall survival (median, 1.2 years vs 1.8 years, P = .02) compared with White patients, indicating that access to similar treatments might not alleviate racial survival disparities.

KEY POINTS

  • After researchers accounted for other variables, self-reported Black race was independently associated with poor survival of patients younger than age 60 years diagnosed with acute myeloid leukemia.
  • Multivariable analyses for outcomes in Black patients did not identify any molecular features associated with achieving complete remission or disease-free survival. However, Black patients harboring FLT3-ITD or IDH2 mutations had shorter overall survival compared with patients who had wild-type disease.
  • Larger prospective studies are needed to establish molecular risk profiles for these patients.

To assess whether any pretreatment features may help to explain the different outcomes, the researchers analyzed the clinical, cytogenetic, and gene-mutation features of the Alliance cohort of patients. They found that compared with young White patients, young Black patients’ leukemic cells had normal cytogenetics less often (38% vs 52%, P = .01), a lower frequency of prognostically favorable NPM1 mutations (25% vs 38%, P = .04), and a higher frequency of IDH2 gene mutations (17% vs 8%, P = .03).

Multivariable analyses for outcomes in younger Black patients did not identify any molecular features associated with achievement of complete remission or disease-free survival. However, Black patients harboring FLT3-ITD or IDH2 mutations had shorter overall survival compared with patients with wild-type disease (FLT3-ITD, HR = 1.95, P = .03; IDH2, HR = 2.17, P = .008).

In multivariable analyses, Black race was associated with worse overall survival compared with White race in the Alliance cohort, with Black patients having a 40% higher likelihood of death compared with White patients (P = .02), after adjustment for white blood cell count, age, and FLT3-ITD and NPM1 mutation status.

Conclusion

“Self-reported [Black] race is the most important patient-associated factor associated with poor survival in patients with AML younger than 60 years of age based on SEER. Survival analyses in Alliance patients identify Black race as an independent poor survival prognosticator in patients with AML besides established molecular markers. This disparity must be urgently addressed to ensure improved outcomes for Black patients with AML, and larger prospective studies to establish molecular risk profiles are needed,” concluded the study authors. 

DISCLOSURE: Dr. Bhatnagar has received research funding from Karyopharm Therapeutics and Cell Therapeutics and has served on advisory committees for Cell Therapeutics, Novartis, Astellas, Pfizer, and Kite Pharma.

REFERENCES

1. American Cancer Society: Cancer Facts & Figures for African Americans 2019–2020. Available at www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/cancer-facts-and-figures-for-african-americans/cancer-facts-and-figures-for-african-americans-2019-2021.pdf. Accessed December 7, 2020.

2. Bhatnagar B, Zhao Q, Fisher JL, et al: Poor treatment outcomes of young (< 60 years) African American patients diagnosed with acute myeloid leukemia (Alliance). 2020 ASH Annual Meeting & Exposition. Abstract 6. Presented December 6, 2020.

3. Bhatnagar B, Kohlschmidt J, Mrozek K, et al: Poor survival and differential impact of genetic features of black patients with acute myeloid leukemia. Cancer Discov. December 4, 2020 (early release online).

 


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