Abstract B114: Population differences in the associations between chromosomal abnormalities and overall survival among Blacks and Whites with multiple myeloma

Abstract

Abstract Background: Several primary and secondary cytogenetic abnormalities (e.g., translocation t(4;14) and 1q copy number changes) are associated with poor prognosis and worse survival of multiple myeloma (MM). Some of the aberrations (e.g., t(11;14), t(14;16), and t(14;20)) have been suggested, albeit inconclusively, to be enriched in Blacks. However, whether the associations between chromosomal abnormalities and overall survival (OS) of MM differ by race/ethnicity remains largely unknown. Methods: We prospectively enrolled 586 patients with newly diagnosed MM between 2010-2019 at the University of Chicago Medical Center. Of the 561 subjects identified as Black or White, 181 had chromosomal abnormalities determined by fluorescence in situ hybridization (FISH), which used CD138+ plasma cells enriched from bone marrow aspirates collected within 180 days of diagnosis. We analyzed data for 19 aberrations, including IGH/FGFR3 fusion [t(4;14)(p16,q32)]; IGH/CCND1 fusion [t(11;14)(q13,q32)]; IGH/MAF [t(14;16)(q32,q23)]; IGH/MAFB [t(14;20)(q32,q12)]; trisomies of chromosome 3, 7, 9, and 12; chromosome 13 deletion; loss of ATM [11q22.3]; gain of ATM; loss of TP53 [17p13.1]; gain of TP53; loss of CDKN2C [1p32.3]; gain of CKS1B [1q21]; IGH translocation with uncommon chromosome partners; IGH locus rearrangement; loss of IGH; and tetraploidy. Vital status was ascertained using the National Death Index. Baseline clinical and laboratory data were retrieved from electronic medical records. We used proportions and Chi-square tests to compare the distributions of cytogenetic abnormalities in Blacks and Whites. In each population, we evaluated the associations between cytogenetic abnormalities and OS using hazard ratios (HRs) and 95% confidence interval (CIs) from Cox proportional hazards models, adjusting for prognostic factors including age, international staging system, elevated lactate dehydrogenase, and estimated glomerular filtration rate. We used the Wald test of the cross-product terms to assess potential heterogeneity of effect in the HRs by race. Results: Of the 181 MM patients, 55 (30.39%) were Black and 126 (69.61%) were White. The median follow-up was 69 months. The frequencies of the 19 cytogenetic abnormalities did not differ between Blacks and Whites. However, we observed population differences in the associations between two chromosomal abnormalities and OS: the presence of t(4;14) was associated with worse OS in Blacks (HR=14.34 [2.17-94.58]; N=38) but not Whites (HR=2.04 [0.70-5.88]; N=99, p-heterogeneity = 0.08), whereas gain of 1q was associated with poorer OS in Whites (HR: 3.38, 95% CI: [1.25- 9.09], N=77), but not Blacks (HR=1.32 [0.31-5.68]; N=32; p-heterogeneity=0.02). Conclusions: Although we found similar frequencies of primary and secondary chromosomal abnormalities between Blacks and Whites, our data show population differences in the associations between two established high-risk cytogenetic abnormalities and the OS of MM. Our findings suggest that cytogenetic features may have varying impacts on the OS of MM based on race. Citation Format: Bei Wang, Benjamin A. Derman, Jason Cheung, Wei Zhang, Andrzej Jakubowiak, Brian C. Chiu. Population differences in the associations between chromosomal abnormalities and overall survival among Blacks and Whites with multiple myeloma [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B114.