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A study found that significant racial disparities exist in mutation profiles among patients with myelofibrosis, highlighting the need for tailored management.

A recent study found significant racial differences in mutations among patients with myelofibrosis (MF), prompting researchers to call for a more proactive approach to management and greater enrollment in clinical trials.

“Our study reveals significant racial disparities in mutation profiles among myelofibrosis patients. Our findings illuminate that some differences exist in genetic mutations in our patient population compared to what has been reported in most research, which has been done in mainly White populations,” study author Swati Goel, MD, tells Physician’s Weekly (PW).

Studies on MF genetic risk factors remain sparse, and the MF cohort in the National Cancer Institute Surveillance, Epidemiology, and End Results database is 82% White.

In what was, to their knowledge, “the first single-center study to investigate racial disparities in genotypes and clinical outcomes in MF in a racially diverse cohort,” Dr. Goel and colleagues retrospectively reviewed the records of 88 patients with MF treated at one site between 2000 and 2023. The site is the only tertiary care center servicing 1.4 million residents of the Bronx, New York, of whom 54.8% are Hispanic and 28.5% are Black.

As reported in Leukemia & Lymphoma, the researchers divided the patients into groups based on race and ethnicity, mutations, other clinically significant data, survival, and leukemic transformation. They found significantly higher prevalence of high molecular risk (HMR) mutations in non-White patients than in White patients, especially in Black and Hispanic cohorts, but they found no differences in leukemic transformation or overall survival between the non-White and White groups.

Dr. Goel and her coauthors, John Yan, MD, and Josette Kamel, MD, talked with PW about their research and how their findings may affect patient care.

PW: How did you discern how race and ethnicity impacted patients with myelofibrosis on a genetic, mutation-specific level?

Dr. Yan: To understand the impact of race and ethnicity on genetic mutations in myelofibrosis, we utilized next-generation sequencing data from a diverse cohort of patients treated at our center. By comparing the presence and frequency of mutations across different ethnic groups, we could discern patterns and prevalence of mutations like JAK2 and HMR, providing a clearer picture of how these genetic factors differ among ethnicities. 

PW: What were your most important findings, and how can they be applied in the clinic?

Dr. Goel: We found that median overall survival was the shortest in the non-Hispanic Black cohort (7.7 years), followed by the non-Hispanic White (8.7 years) and Hispanic cohorts (9.4 years). This was not statistically significant given our small sample size. In terms of mutations, non-Hispanic White patients had the highest proportion of JAK2 (82%), while Asians had the highest proportion of CALR (60%).

Non-Hispanic Black and Hispanic patients had higher proportions of previously described high molecular risk mutations: 53% of non-Hispanic Black patients and 60% of Hispanic patients had HMR mutations ASXL1, SRSF2, U2AF1, EZH2, and IDH1/2, compared to 21% of non-Hispanic White patients and no Asian patients. SRSF2 was the only HMR mutation we identified to be negatively prognostic in our non-White cohort, though IDH1/2, EZH2, and U2AF1 showed a trend toward poorer survival.

TP-53, though not categorized as an HMR mutation in MF prognostic models, was most strongly associated with worse survival in our non-White cohort. TP-53 should be considered a high-risk mutation, and patients with this mutation should be evaluated for bone marrow transplant or clinical trials as early as possible.

Dr. Yan: Our findings can help refine prognostic models and tailor myelofibrosis therapeutic approaches. Knowing that certain high-risk mutations are more prevalent in specific ethnic groups could lead to more personalized monitoring and treatment strategies, especially in diverse populations. Clinicians might, for example, consider more aggressive surveillance for HMR mutations in Black and Hispanic patients, given their higher prevalence in these groups.

PW: Did your results surprise you?

Dr. Goel: Some results were surprising. ASXL1 is considered a poor prognostic mutation, but this was not the case in our patient cohort. Similarly, TP-53, which is not included in the prognostic scoring, showed the worst prognosis.

PW: Why was it urgent to study myelofibrosis across ethnic populations?

Dr. Kamel: We conducted this study to address a significant gap in our understanding of myelofibrosis across different ethnicities. Given the increasing recognition of healthcare disparities, particularly in underrepresented populations, our research adds insights that could lead to more equitable healthcare initiatives, such as improving inclusivity in clinical trials.

PW: What questions remain unanswered for you?

Dr. Goel: More myelofibrosis work needs to be done worldwide to understand the effects of race, ethnicity, socioeconomic status, and other factors. Our study was modest in sample size, and larger studies that include all races and ethnicities are needed.

Dr. Kamel: Future work is warranted to elucidate the exact mechanisms by which these mutations influence disease progression in different ethnic groups. Further research with larger, multi-center cohorts is needed to validate our findings and to conduct multivariate analyses to elucidate other potential confounders.

PW: What else should clinicians keep in mind as they treat patients with myelofibrosis?

Dr. Goel: Please encourage as much participation as possible in clinical trials for diseases like myelofibrosis. Clinical trials should not only be for patients of higher socioeconomic status.