Introduction Multiple myeloma (MM) is a hematological malignancy characterized by clonal proliferation of plasma cells within bone marrow. It is one of the most common hematologic malignancies in high-income countries and is often associated with significant morbidity due to end-organ damage. Over the past two decades, the introduction of novel therapies has significantly transformed the treatment landscape. This study aims to evaluate the impact of these therapeutic advances on mortality trends while highlighting persistent disparities in MM-related deaths in the United States (U.S.) adults.

Methods We analyzed national mortality data from the CDC WONDER database (1999–2023) using ICD-10 code C90.0 for multiple myeloma-related deaths among U.S. adults. Age-adjusted mortality rates (AAMRs) were calculated per 100,000 population; stratified by sex, age groups, census regions, and race/ethnicity. Age was stratified into three groups: older adults (≥ 65 years), middle-aged adults (45-64 years), and younger adults (25-44 years). Temporal trends were assessed using Joinpoint regression (v5.0) that identified inflection points and calculated average annual percent changes (AAPCs) and annual percent changes (APCs); a p-value <0.05 was considered statistically significant.

Results From 1999 to 2023, a total of 283614 MM-related deaths were reported in the U.S. adult population. Overall, the average AAMR was 5.12, significantly declining from 5.89 in 1999 to 4.96 in 2023 (AAPC: -1.54, p-value: 0.001). From 1999 to 2002, there was a non-significant decline in AAMR (APC: -0.59, p-value: 0.29), followed by a significant decline from 2002 to 2009 (APC: -1.99, p-value: 0.04). This was followed by a non-significant rise from 2009 to 2012 (APC:1.10, p-value: 0.08), then a significant decline from 2012 to 2021 (APC: -1.50, p-value: 0.001), and finally a recent highest significant decline from 2021 to 2023 (APC: -5.35, p-value: 0.001).

Males had higher AAMR than females throughout, 7.21 vs 5.0 in 1999 and 5.03 vs 3.37 in 2023. Females experienced a greater reduction (AAPC: -1.67, p-value: 0.001) than males (AAPC: -1.51, p-value: 0.001).

Older adults had the highest average AAMR (21.04), followed by middle-aged adults (2.78) and younger adults (0.13). The highest reduction in AAMR was observed in middle-aged adults (AAPC: -2.81, p-value: 0.001), followed by younger adults (-2.44, p-value: 0.001) and older adults (AAPC: -1.30, p-value: 0.001).

Census-based analysis showed the highest average AAMR observed in the Midwest and the South (5.36), followed by the Northeast (4.83) and the West (4.77). Highest reduction in AAMR was seen in the Northeast (AAPC: -1.81, p-value: 0.001), followed by the West (AAPC: -1.54, p-value: 0.001), then the Midwest (AAPC: -1.50, p-value: 0.001), and the South (AAPC: -1.50, p-value: 0.001).

Race-based analysis showed that non-Hispanic (NH) Black/African American had the highest average AAMR (9.84), followed by NH White (4.78), NH American Indian/Alaska Native (4.33), Hispanic/Latino (4.24), and NH Asian/Pacific Islander (2.48). Highest reduction in AAMR was observed in NH American/Indian/Alaska Native (AAPC: -2.00, p-value: 0.005), followed by NH Black/African American (AAPC: -1.51, p-value: 0.001), NH White (AAPC: -1.42, p-value: 0.001), Hispanic/Latino (AAPC: -1.32, p-value: 0.001), and NH Asian/Pacific Islander (AAPC: -1.13, p-value: 0.001).

Conclusion Although overall mortality has significantly decreased over the past two decades, disparities still exist across demographics; male, older adults, NH Black/African Americans, and residents of the Midwest and South carry the highest mortality burden. As treatments continue to advance, future studies should include patient populations that reflect the broader demographic landscape, especially racial minorities and the elderly, to ensure equitable outcomes.

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2025
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