Clinical Context

There are approximately 20,000 new cases of AML diagnosed in the US each year, which makes it the most common form of acute leukemia. The authors of the current study provide a review of outcomes of AML. From 20% to 30% of patients with AML never achieve complete remission after intensive frontline treatment. Beyond that, half of patients relapse after achieving complete remission, which usually occurs from 2 to 3 years after diagnosis. Age 60 years or older is a significant risk factor for worse survival in AML.

Some studies have also demonstrated that Black race is associated with worse outcomes of AML. The current study compares survival and remission data among Black and White adults with AML.

Study Synopsis and Perspective

Black race is the most important risk factor for patients with acute myeloid leukemia (AML) and is associated with poor survival, according to new findings.

Among patients with AML younger than 60 years, the rate of overall 3-year survival was significantly less among Black patients than White patients (34% vs 43%). The risk for death was 27% higher for Black patients compared with White patients.

"Our study demonstrates the delicate interplay between a variety of factors that influence survival disparities, particularly for younger Black AML patients," said first author Bhavana Bhatnagar, DO, from Ohio State University's Comprehensive Cancer Center in Columbus. "We were able to confirm the impact of socioeconomic factors while also demonstrating that being Black is in and of itself an independent poor prognostic variable for survival."

The findings of the study were presented during the plenary session of the annual meeting of the American Society of Hematology, which was held online this year. The study was simultaneously published in Cancer Discovery.

Racial disparities in cancer outcomes remain a challenge. The term "health disparities" describes the differences of health outcomes among different groups, commented Chancellor Donald, MD, from Tulane University School of Medicine, New Orleans, Louisiana, who introduced the article at the meeting. "Racial health disparities usually result from an unequal distribution of power and resources, not genetics.

"The examination of health disparities is certainly a worthwhile endeavor," he continued. "For generations, differences in key health outcomes have negatively impacted the quality of life and shortened the lifespan of countless individuals. As scientists, clinicians, and invested members of our shared society, we are obligated to obtain a profound understanding of the mechanisms and impact of this morbid reality."

Black Race a Risk Factor

For their study, Dr Bhatnagar and colleagues conducted a nationwide population analysis using data from the Surveillance Epidemiology End Results (SEER) Program of the National Cancer Institute to identify 9430 adults aged 18 to 60 years who were diagnosed with AML between 1986 and 2015.

To characterize molecular features, targeted sequencing of 81 genes was conducted in 1339 patients with AML who were treated on frontline Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology (Alliance) protocols based on standard intensity cytarabine/anthracycline induction followed by consolidation between 1986 and 2016. None of these patients received an allogeneic stem cell transplant when they achieved complete remission.

Although overall survival has improved during the past 3 decades, survival disparities between Black and White patients has widened over time (P<.001). The authors found a nonstatistically significant difference in survival between 1986 and 1995 (White patients, n=1365; Black patients, n=160; P=.19). However, the difference was significant between 1996 and 2005 (White patients, n=2994; Black patients, n=480; PP<.001). "And it became even more noticeable in the most recent decade," said Dr Bhatnagar. "Furthermore, younger Black AML patients were found to have worse survival compared to younger White AML patients."

Results from the second analysis of patients treated on Alliance protocols did not show any significant differences in early death rates (10% vs 6%; P=.20) and complete remission rates (71% vs 71%; P=1.00). "While relapse rates were slightly higher in Black compared to White patients; this difference did not reach statistical significance," said Dr Bhatnagar. "Additionally, there was also no significant difference in the number of cycles of consolidation chemotherapy administered to these patients."

However, both disease-free and overall survival were significantly worse for Black patients, suggesting that factors other than treatment selection were likely at play in influencing the survival disparity. The median disease-free survival for Black patients was 0.8 years vs 1.4 years for White patients (P=.02). Overall survival was 1.2 years vs 1.8 years (P=.02).

Relapse rates were slightly higher in Black patients than in White patients, at 71% vs 59%, but this difference did not reach statistical significance (P=.14).

Differences in Biomarkers

With regard to underlying molecular differences between Black and White patients, the investigators found that the most common mutations were in NPM1, FLT3-ITD, and DNM3TA. Mutations were detected in more than 20% of Black patients. Other commonly mutated genes were IDH2, NRAS, TET2, IDH1, and TP53, which were mutated in more than 10% of patients. "All of these genes are established commonly mutated genes in AML," said Dr Bhatnagar.

On univariable and multivariable outcome analyses, which were used to identify clinical or molecular features that had a bearing on outcome, the presence of FLT3-ITD and IDH2 mutations were identified as the only mutations associated with a higher risk for death in Black patients. "This is actually a very important finding, as both FLT3 and IDH2 are now targetable with small-molecule inhibitors," said Dr Bhatnagar. "In addition, it is also worth noting that other gene mutations that have known prognostic significance in AML, such as NPM1, as well as RUNX1 and TP53, did not remain in the final statistical model.

"Importantly, our study provides powerful evidence that suggests differences in underlying disease biology between young Black and White AML patients, as evidenced by differences in the frequencies of recurrent gene mutations, " she said.

Understudied Disparities

Although the study showed that Black patients had worse outcomes, "surprisingly, the authors found these outcomes hold even when the patients are participating in clinical trials," noted Elisa Weiss, PhD, senior vice president of education, services and health research for the Leukemia and Lymphoma Society.

"The study makes clear that the medical and science community need to do more to better understand the social, economic, environmental, and biological causes of these disparities," she told Medscape Medical News. "In fact, the findings suggest that there are myriad complex and understudied causes of the identified disparities, and they are likely to lie at the intersection of all levels of the social ecology that impact an individual's ability to access timely and unbiased care, maintain their mental and physical health, and receive needed social support and resources." She noted that the Leukemia and Lymphoma Society has an Equity in Access research program that aims to "advance study of underlying causes of inequitable access to care and identify policies, strategies, and interventions that have the potential to reduce inequities and increase access to healthcare, services, and programs for blood cancer patients and survivors."

The research was supported in part by the National Cancer Institute of the National Institutes of Health and other institutions and through several scholar awards. Dr Bhatnagar has received advisory board honoraria from Novartis, Kite Pharma, Celgene, Astellas, and Cell Therapeutics. Dr Weiss has disclosed no relevant financial relationships.

American Society of Hematology (ASH) 2020 Annual Meeting: Abstract 6. Presented December 6, 2020.^[1]

Cancer Discov. Published on December 4, 2020.^[2]

Clinical Implications

• AML is the most common acute leukemia among US adults. From 20% to 30% of patients with AML never achieve complete remission after intensive frontline treatment. Beyond that, half of patients relapse after achieving complete remission, and relapse usually occurs from 2 to 3 years after diagnosis. Age 60 years or older is a significant risk factor for worse survival in AML.
• The current study demonstrates that Black patients with AML have reduced survival compared with White patients, particularly at age younger than 60 years and in the presence of the NPM1 mutation. An analysis based on similar induction therapy among Black and White patients confirmed the lower survival rate among Black patients.
• The current study highlights the disparity in acute myeloid leukemia survival outcomes among Black and White patients. The healthcare team should account for the difference in survival rates associated with the NPM1 mutation in Black and White patients.

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