Abstract
Introduction Immune dysregulation is a hallmark of multiple myeloma (MM), characterized by impaired humoral immunity and increased expression of immunosuppressive cytokines such as IL-10 and TGF. When combined with therapy-induced immunosuppression, this effect significantly elevates susceptibility to infections and sepsis. Diagnosing sepsis in MM patients is often challenging due to the overlapping clinical features of the disease and infection. Despite medical advances, sepsis remains the most common cause of hospitalization and mortality in this population. This study aims to analyze national trends and disparities in sepsis-related mortality among MM patients to inform targeted prevention and care strategies.
Methods We utilized the CDC WONDER Multiple Cause of Death database to assess trends in sepsis-related mortality (ICD-10 codes: A40, A41) among adult patients aged 25 years and older with Multiple Myeloma (ICD-10 codes: C90) from 1999 to 2020. Age-adjusted mortality rates (AAMRs) per 100,000 population and Crude Rates (CRs) were calculated across subgroups defined by age, sex, race/ethnicity, state, place of death, census region, and urbanization level. The Joinpoint Regression Program was used to estimate annual percentage changes (APCs), average annual percentage changes (AAPCs), and corresponding 95% confidence intervals (CIs).
Results A total of 24,184 sepsis-related deaths among individuals with MM were recorded from 1999 to 2020. Most of these deaths occurred in medical facilities (90%), followed by the decedent's home (3.4%), nursing homes (3%), and hospice facilities (2.5%). The overall AAMR decreased from 0.55 in 1999 to 0.46 in 2020 with an AAPC of –0.87 (95% CI: –1.35 to –0.4). Men had consistently higher AAMR than women (overall AAMR for men: 0.62 vs. women: 0.39). Declines in AAMR were observed in both men (0.73 to 0.59; AAPC: –1.15, 95% CI: –2.3 to 0.013) and women (0.45 to 0.33; AAPC: –1.27, 95% CI: –1.72 to –0.83). Individuals aged 75-84 years had the highest crude mortality rate of 2.23 per 100,000, accounting for over 28% of all deaths. Among racial groups, Non-Hispanic (NH) Black individuals had the highest AAMRs throughout the study period. However, both NH Black and NH White populations experienced decline (NH Black: 1.52 to 1.1; AAPC: –1.55, 95% CI: –2.34 to –0.74) (NH White: 0.46 to 0.37; AAPC: –0.93, 95% CI: –1.35 to –0.51). AAMRs also varied slightly by region, with the highest rates in the Northeast (0.53) and South (0.5), followed by the Midwest (0.46) and the West (0.45). Urban areas had the highest overall AAMR (0.5) compared to rural areas (0.45), reflecting a modest urban-rural disparity. States in the top 90th percentile of sepsis and MM-related mortality were the District of Columbia, Mississippi, South Carolina, Maryland, and New Jersey, each exhibiting approximately double the AAMRs compared to states in the lowest 10th percentile.
Conclusion There is an overall decrease in trends for sepsis-related deaths recorded in MM from 1999 to 2020 in the United States. Still, significant disparities exist across age, race, sex, place of death, urbanization, and geographic distribution. Mortality rates are noted to be disproportionately higher amongst the elderly population, men, and NH Black. Geographically, higher mortality rates were observed in the Northeastern and urban regions of the United States. These inequities in mortality trends highlight the importance of urgent multidisciplinary interventions to address the causes and reduce sepsis-related mortality in multiple myeloma patients.
