It has been well documented that, collectively, Black individuals have the highest death rate and shortest survival of any racial/ethnic group in the United States for most cancers. Black men also have the highest cancer incidence. Although the causes of these inequities are complex, a study by Bhavana Bhatnagar, DO, and colleagues investigating the outcomes of adult patients with acute myeloid leukemia (AML) and characterizing molecular features of the cancer in Black patients compared with White patients has found after accounting for other variables, the strongest factor associated with poor survival in patients younger than 60 years diagnosed with AML was self-reported Black race. There is urgent need to address this survival disparity in Black patients and to conduct larger studies to establish molecular risk profiles of these patients, according to the study authors. These findings were presented at a press briefing in advance of the 2020 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 6).

Bhavana Bhatnagar, DO

“Survival among young Black people with AML is strikingly and unacceptably worse than what we see in white patients with AML, particularly in younger patients,” said first author Dr. Bhatnagar, of The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, in an ASH press release. “When we looked specifically at the mutations we see in AML, even when Black patients have specific good prognostic risk factors, they had poorer outcomes.”

Study Methodology

The researchers used data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute to identify 11,190 adults age 18–60 diagnosed with AML (excluding acute promyelocytic leukemia) between 1986 and 2015. To characterize molecular features, the researchers performed targeted sequencing of 81 genes in 1,339 patients treated on frontline 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 2016. No Alliance patient received an allogeneic stem cell transplant in the first complete remission.

Study Results

The researchers found that while there was a slightly higher risk of death for men (hazard ratio [HR] = 1.09) and a lower risk of death for patients with a higher median household income (> $79,6000 vs < $54,400; HR = 0.85), after accounting for other variables in the model, the strongest factor affecting survival of these patients was self-reported race. Specifically, Black patients had a higher risk of death compared with White patients (HR = 1.28), with 3-year overall survival rates of 32% and 41%, respectively (P < .001).

To evaluate if this race-associated survival disparity also persisted in patients 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, 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.

To assess whether any race-associated pretreatment features may help explain the different outcomes, the researchers analyzed the clinical, cytogenetic, and genetic mutation features of the Alliance cohort. Compared to White patients, they found that Black patients’ tumors had normal cytogenetics less often (38% vs 51%, P = .01), lower frequency of prognostically favorable NPM1 mutations (25% vs 38%, P = .04), and higher frequencies of spliceosome gene mutations (24% vs 12%, P = .009).

Multivariable analyses for outcome in Black patients did not identify any molecular features associated with achievement of complete remission or disease-free survival. However, Black patients with tumors harboring FLT3-ITD or IDH2 mutations had shorter overall survival compared with patients with FLT3 wild-type disease (FLT3-ITD: HR = 1.95, P = .03; IDH2: HR = 2.17, P = .008). Notably, other well-established mutational features known to associate with outcome (for example, NPM1 or TP53 mutations) did not impact survival.

In addition, the researchers performed univariable and multivariable outcome analyses for overall survival in the Alliance patients. They found that having NPM1-mutated tumors and non-Black race were the only positive prognostic factors associated with longer overall survival in the final risk model (NPM1-mutated vs wild-type: HR=0.72, P < .001; White vs Black: HR = 0.72, P = .03).

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

Dr. Bhatnagar added, “It was notable that several of the mutations that have known prognostic impact in [patients with] AML as a whole—and that we typically use to classify patients’ disease—do not seem to carry the same prognostic relevance for younger Black patients,” said Dr. Bhatnagar. “Furthermore, when we looked at all younger [patients with] AML, Black race was an independent predictor of poor outcome in both the SEER and Alliance data sets. This suggests that Black race by itself seems to be such a strong risk factor that it adds to the markers we usually rely on to risk-stratify patients.”

Disclosure: For full disclosures of the study authors, visit ash.confex.com.