Abstract 2261: Distinct genomic and high-risk cytogenetic features in black multiple myeloma patients: Insights from the PE-CGS Network

Abstract Introduction: Landmark cancer genome sequencing programs have significantly advanced cancer research, leading to novel therapies and preventive strategies. However, the underrepresentation of racial minority groups in these studies limits the applicability of findings and leaves critical gaps in understanding cancer disparities. The Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network, established under the National Cancer Institute’s Cancer Moonshot, seeks to address these gaps by engaging with understudied populations. Multiple myeloma (MM), which disproportionately affects Black patients with higher incidence, exemplifies the need for inclusive research. High-risk cytogenetic events are strongly associated with poor outcomes in MM but are not well characterized in Black patients due to limited data. To address these disparities, we analyzed the genomic landscape of Black MM patients recruited through the PE-CGS Network. Methods: A total of 191 self-reported Black MM patients (59% female, aged 41-98 years, median: 66) were recruited. Whole-exome sequencing was performed on 124 tumor-normal paired samples, including 83 newly diagnosed MM (NDMM), 20 plasmacytoma, and 21 relapsed/refractory MM (RRMM) cases. We conducted a 1:2 matched case-control study comparing Black NDMM patients from the PE-CGS study with White NDMM patients from MMRF CoMMpass study, matched by age and sex, to identify genomic differences between two groups. Three high-risk cytogenetic events, del(17p), del(1p) and gain(1q), were assessed in both groups. Copy number variants (CNVs) were categorized based on the tumor-to-normal copy number ratio as high amplification (≥4 copies), gain (>2.5 & <4 copies), deletion (<1.5 copies), or neutral (1.5-2.5 copies). Results: Among 124 tumor samples from Black MM patients, 36.4% harbored at least one high-risk cytogenetic event. In the 83 tumor samples from Black NDMM patients, del(17p) occurred in 22.3%. High amplification of 1q was present in 25.30% of Black patients, higher than 8.04% in White patients. Del(1p) was observed in 18.18% of tumors from Black patients. Somatic mutation analysis revealed that KRAS (22.1%) and NRAS (15.6%) were the most frequently mutated genes among Black patients. TP53 mutations were observed in 5.7% of Black patients, exceeding previously reported frequencies. TP53 CNVs varied by self-identified race, with high amplification more frequent in White (30.36%) than Black patients (1.61%). Conclusions: In this study, we highlight the distinct genomic landscape in Black MM patients, including higher rate of high-risk cytogenetic events and unique mutational patterns compared to Whites. These findings underscore the importance of engaging underrepresented populations in cancer research, as exemplified by the PE-CGS Network, to improve risk stratification and advance equitable healthcare outcomes. Citation Format: Yizhe Song, Reyka G. Jayasinghe, Mark Fiala, Michael J. Slade, Song Cao, Fernanda Martins Rodrigues, R. Jay Mashl, Erin Linnenbringer, Bailey Martin-Giacalone, Yingduo Song, Erik Storrs, Chien-Wei Peng, Fankun Zeng, Hasani Bland, Danielle Grasso, Julie Fortier, Zachary Crees, Robert S. Fulton, Shelly O'Laughlin, Tracie L. Deluca, Eric J. Duncavage, David H. Spencer, Ravi Vij, Kiran Vij, Bettina F. Drake, Ryan C. Fields, Graham A. Colditz, Li Ding. Distinct genomic and high-risk cytogenetic features in black multiple myeloma patients: Insights from the PE-CGS Network [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2261.