Molecular and cytogenetic landscape of black patients with myelodysplastic syndrome in the veterans health affairs

Abstract

Abstract Introduction: Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders characterized by ineffective hematopoiesis, cytopenias, and increased risk of acute myeloid leukemia (AML). While racial disparities in clinical outcomes are well documented in AML, there is limited genomic and clinical data specific to Black patients (pts) with MDS. The primary objective was to characterize the cytogenetic, molecular, and clinical features of Black pts with MDS. Secondary objective was to determine the overall survival (OS). Methods: We conducted a retrospective cohort study of 840 pts diagnosed with MDS between 2017 and 2025 across the national Veterans Health Affairs (VA) healthcare system. Pts were stratified by self-reported race into Black (n=304) and non-Black (n=536) groups. Risk stratification was performed using both the Revised International Prognostic Scoring System (IPSS-R) and the Molecular IPSS (IPSS-M) when applicable. We performed chart review to obtain history of hypomethylating agents therapy (HMA), time to treatment, AML transformation and allogeneic stem cell transplantation (SCT). Pts with no available racial or IPSS-R stratification data were excluded. Results: The median age at diagnosis for Black and non-Black patients was 73 years [IQR 68-79] vs. 76 years [IQR 77-82], p=0.187, respectively. Black pts had a higher proportion of diagnoses <65 years (17% vs. 9%, p<0.001), while non-Black pts more frequently presented at older age (≥75 years) (43% Black vs. 60% non-Black, p=<0.001). Therapy-related MDS (t-MDS) was more common in Black pts (17% vs. 10%, p=0.006). Complex cytogenetics were similar (18% in Black vs. 19% in non-Black pts), with a trend toward a higher frequency of del (7)/-7 among Black pts (18% vs. 13%, p=0.053). Targeted next-generation sequencing (NGS) data were available in 60% of pts, with at least one somatic mutation detected in 88%. Certain alterations were more common in Black pts, including ASXL1 (29% vs. 20%, p=0.031), DNMT3A (15% vs. 8%, p=0.029), NRAS (4% vs. 1%, p=0.016), and PTPN11 (2% vs. 0%, p=0.034), particularly among older pts. Non-Black pts more commonly had SRSF2 (17% vs. 10%, p=0.029) and SF3B1 (19% vs. 11%, p=0.024) mutations. The prevalence of SF3B1 was similar between younger Black and non-Black patients (27% vs. 26%). TP53 mutations (19% vs. 19%) and MDS-biTP53 rates (8% vs. 7%) did not significantly differ. There were no significant differences in the IPSS-R or IPSS-M risk stratification between the groups, with similar rates of high-risk MDS (53% Black vs. 52% non-Black). A total of 285 pts received HMA (34% both groups) with a median time to treatment initiation of 1.6 months (1.5 vs. 1.7 months, p=0.940). Black pts had a higher rate of AML transformation (14% vs. 7%, p=0.002). Overall, 3% proceed to allogeneic SCT (2% Black vs. 4% non-Black, p=0.236). With a median follow-up of 41 months, the OS showed no significant differences with a median OS of 22 months for Black vs. 24 months for non-Black pts (p=0.832). OS was similar when grouped by MDS risk group, with an OS of 12 months vs. 14 months (p=0.522) for high-risk MDS pts and 45 months vs. 40 months (p=0.515) for Black vs. non-Black pts with low-risk MDS, respectively. Among older pts, Black pts had significantly worse survival with a median OS of 23 months vs. 33 months (p=0.044). Conclusion: In this large national VA cohort, we identify distinct clinical and biological features of Black pts with MDS, including younger age at diagnosis, higher prevalence of t-MDS, increased frequency of del (7)/-7, and greater rates of AML transformation. NGS revealed enrichment of high-risk mutations such as ASXL1, DNMT3A, NRAS, and PTPN11 in older Black pts, while SF3B1 and SRSF2 mutations were more common in non-Black pts. In the VA where there is more equal access to care, there was no difference in overall survival across racial groups. These findings highlight the importance of inclusive genomic profiling in refining risk stratification and treatment decisions in MDS. An ongoing analysis is evaluating predictors of response and the associations between biological, cytogenetic, and molecular features and survival outcomes in Black pts with MDS. The research reported was supported by the Washington University ICTS grant UL1TR002345 from the National Center for Advancing Translational Sciences of the NIH. The content is solely the responsibility of the authors and does not necessarily represent the official view of the NIH.