Background:

Multiple myeloma (MM) is associated with severe immunosuppression, increasing the risk of infection-related mortality. Sepsis is a major cause of death in MM patients, but large-scale, population-based trends in sepsis-specific mortality among this group remain underexplored.

Objectives:

To evaluate temporal and demographic patterns in sepsis-specific mortality among U.S. adults aged ≥35 years with concurrent MM from 1999 to 2023.

Methods:

We analyzed CDC WONDER Multiple Cause of Death data for individuals aged ≥35 years with deaths listed as due to both MM (ICD-10 C90.0–C90.2) and septicemia (ICD-10 A41.0–A41.5, A41.8, A41.9) from 1999–2023. Age-adjusted mortality rates (AAMRs) were calculated using the 2000 U.S. standard population. Temporal trends were analyzed using Joinpoint regression to estimate annual percentage changes (APCs). Analyses were stratified by age, sex, residence, and year. Average annual percent change (AAPC) and annual percent change (APC) were calculated, with 95% confidence intervals (CIs). All the data used in this study are publicly available at (wonder.cdc.gov). This study complies with STROBE guidelines.

Results:

From 1999 to 2023, 29,612 sepsis-related deaths were recorded among U.S. adults with multiple myeloma. While the absolute number of deaths rose from 973 in 1999 to a peak of 1,411 in 2022, age-adjusted mortality rates (AAMR) declined overall, from 0.68 to 0.55 per 100,000. Female mortality declined steadily (APC = –1.11%/year, p<0.05), whereas male trends were more variable, with alternating periods of decline and increase; male rates consistently exceeded female rates. Urbanization analysis revealed the highest mortality in large central metros, which declined significantly (APC = –1.01%), while rural areas remained largely unchanged. Age-stratified trends showed significant declines in adults 45–74 years, a temporary spike followed by decline in ages 75–84, and a persistent increase among adults ≥85 years (APC = +0.96%). Regionally, the Northeast experienced the steepest early decline (APC = –2.93% through 2013) but rebounded thereafter, whereas the Midwest and South declined more gradually, and the West remained stagnant. Confidence intervals were narrow and standard errors low, confirming the robustness of estimates. Overall, sepsis-specific mortality declined in most demographic and regional subgroups, though disparities emerged among the oldest adults, rural areas, and certain metropolitan regions after 2013.

Conclusion:While sepsis-specific mortality among U.S. adults with multiple myeloma has declined overall since 1999, especially in younger age groups and urban centers, persistent and emerging disparities remain. Notably, mortality rates have plateaued or increased among the oldest adults, males, rural residents, and select geographic regions in recent years. These findings highlight the need for targeted infection prevention and sepsis management strategies to address vulnerable populations within the MM community.

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2025
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