Black race an independent predictor of poor survival among young adults with AML
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Black young adults with favorable molecular-risk acute myeloid leukemia had poorer survival outcomes than their white counterparts, according to study results presented at the virtual ASH Annual Meeting and Exposition.
These patients therefore may need to be considered for more intensive consolidation, Ann-Kathrin Eisfeld, MD, assistant professor in the division of hematology at The Ohio State University, told Healio.
“It is simply not known whether genetic markers, such as gene mutations, are the same or different in patients with AML with different racial backgrounds and whether these markers carry the same importance, since all large studies have either been solely based on white patients or did not separately analyze data with respect to race,” Eisfeld said.
Eisfeld and Bhavana Bhatnagar, DO, associate professor of medicine in the division of hematology at The Ohio State University, initially worked independently to look more closely at survival disparities among patients with AML, Bhatnagar told Healio.
“While Dr. Eisfeld had spent quite some time examining the potential underlying differences in disease biology between Black patients and white patients, I was exploring various demographic and socioeconomic characteristics of [patients with AML] who were included in the SEER registry and trying to correlate these characteristics with survival,” Bhatnagar said. “Once we reviewed all data, we recognized that the Alliance for Clinical Trials in Oncology protocols data strengthened the SEER data and vice versa, prompting us to join forces and create this larger, more compelling research project.”
Bhatnagar, Eisfeld and colleagues conducted a nationwide population analysis to assess outcomes of adults with AML and then sought to further characterize the molecular features of Black patients vs. white patients.
The researchers derived data from the SEER database on 11,190 adults aged 18 to 60 years diagnosed with AML between 1986 and 2015. They also gathered data on a subset of 1,339 patients with AML treated on front-line Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology protocols. Researchers performed targeted sequencing of 81 genes to characterize molecular features among these patients, none of whom received allogeneic stem cell transplantation in first remission.
Results of the SEER data analysis showed a slightly elevated risk for death among men (HR = 1.09; 95% CI, 1.04-1.15) and a lower risk for death among patients with a higher median household income (> $79,600 vs. < $54,400; HR = 0.85; 95% CI, 0.78-0.94).
However, the strongest risk factor was patient-reported race, with Black adults at higher risk for death than their white counterparts (HR = 1.28; 95% CI, 1.2-1.37). Three-year OS rates were 34% for Black patients vs. 43% for white patients (P < .001).
Results of the Alliance protocols data analysis showed Black patients had inferior DFS (median, 0.8 years vs. 1.4 years; P = .02) and OS (median, 1.2 years vs. 1.8 years; P = .02) than white patients. In addition, Black patients were less likely to have normal cytogenetics (38% vs. 51%; P = .01) and had a lower frequency of prognostically favorable NPM1 mutations (25% vs. 38%; P = .04) and a higher frequency of spliceosome gene mutations (24% vs. 12%; P = .009).
Multivariable analyses showed shorter OS among Black patients who harbored FLT3-ITD mutations (HR = 1.95; P = .03) or IDH2 mutations (HR = 2.17; P = .008) vs. patients with wild-type disease. Further, results of univariable and multivariable OS analyses showed having an NPM1 mutation (HR = 0.72; P < .001) and white race (HR = 0.72; P = .03) were the only prognostic factors linked to increased OS in the final risk model.
“There are, indeed, some important differences in AML disease biology in young Black patients compared with young white patients,” Bhatnagar said. “We have shown that many well-established gene mutations that have known prognostic significance in [patients with AML] may not associate with the same prognostic impact in young Black patients. As such, these patients may need to be managed differently.
“In addition, it is interesting that in both data sets, young Black patients had worse OS than white patients, and in the Alliance data set especially,” Bhatnagar said. “This is intriguing, because the remission rates following similar treatment was not different between the two groups. In addition to differences in disease biology, it is critically important to take socioeconomic factors and access to care into account.”
Validation of the findings in an even larger cohort will be crucial, Eisfeld added.
“The study will need to be expanded further both in its molecular depths, such as looking at additional genes, understanding the actual underlying biology, and also in the comprehensiveness of the factors that we have been assessing, such as taking into account patients’ comorbidities or specifically looking at the impact of bone marrow transplant,” Eisfeld said.
Perspective
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Asya Varshavsky-Yanovsky, MD, PhD
Despite multiple advances in AML therapies, for many patients the prognosis remains poor. To further elucidate reasons behind survival differences between Black and white patients, the investigators evaluated outcomes of patients treated on various Alliance trials, where all patients were given uniform therapies and had the same access to care.
Even in the clinical trials setting, Black patients had inferior EFS and OS compared with whites, indicating more aggressive disease biology. Interestingly, there were no differences in complete response rate. Of note, the patients in the Alliance cohort were not treated with transplant in first complete response; therefore, the comparative benefit of allogeneic transplant was not evaluated in this cohort, and transplant may potentially offer a more effective consolidative strategy for this high-risk population.
The findings of the significantly worse outcomes among Black patients with AML, in the era of modern therapies, and even in the clinical trial setting, requires major intervention on multiple levels. Future research is required to understand molecular mechanisms behind the more aggressive disease course in Black patients in order to tailor optimal induction and consolidation strategies for those patients. In addition, efforts are needed to ensure equal access to high-level care, including allogeneic transplant.
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Bhatnagar B, et al. Abstract 6. Presented at: ASH Annual Meeting and Exposition (virtual meeting); Dec. 5-8, 2020.
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