Introduction: The incidence of multiple myeloma (MM) in the USA has been increasing over the past decades with persistent demographic disparities. Social determinants of health (SDOH) were found to affect health outcomes among certain diseases. However, there were limited data on the impact of SDOH on the MM mortality rates. Our study aimed to investigate the association between the SDOH and MM mortality rates from 2016 to 2020. Methods: County-level data from the Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry Social Vulnerability Index (CDC/ATSDR SVI) were correlated with MM mortality rates from the CDC WONDER database. Counties were categorized into four quartiles based on SVI scores: SVI-Q1 (lowest vulnerability) to SVI-Q4 (highest vulnerability). Age-adjusted mortality rates (AAMRs) per 100,000 individuals for patients aged 25 years and above were analyzed. The rate ratio (RR) was measured by calculating the ratio of the AAMRs in SVI-Q4 to SVI-Q1. Results: Between 2016 and 2020, 61,307 MM-related deaths occurred, with 20,390 in SVI-Q4 versus 8,498 in SVI-Q1. Overall, AAMR was higher in SVI-Q4 (4.90; 95% CI, 4.83–4.97) than in SVI-Q1 (4.66; 95% CI, 4.56–4.76), though the RR was not significant (1.05; 95% CI, 0.81–1.36). Higher SVI was not significantly associated with higher AAMR among males (RR: 1.03; 95% CI, 0.73–1.45) or females (RR: 1.10; 95% CI, 0.75–1.62). Among the younger patients (25–64 years old) and the older patients (65 years old and above), increasing SVI was not associated with higher AAMR (RR: 1.27 [95% CI, 0.69–2.34] and 1.01 [95% CI, 0.76–1.34], respectively). SVI was also not significantly associated with higher AAMR in the rural populations (1.07 [95% CI, 0.60–1.92]). Across racial groups – American Indians, Asians, African Americans, Hispanics, and Whites – SVI was not significantly associated with AAMR differences. Similarly, no significant differences were observed when stratified by census regions (Northeast, Midwest, South, and West). Conclusion: African Americans had higher AAMRs from MM compared to other racial groups. However, SVI scores were not significantly associated with MM mortality disparities. These findings suggest that SVI alone is insufficient to determine mortality disparities in MM. Future research should explore more specific indicators to identify at-risk populations and address mortality inequities in MM.

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