Evolving mortality trends in waldenstrom marcroglobulinemia: A 21 year analysis (1999-2020) using the CDC WONDER database.

e22546 Background: Waldenström Macroglobulinemia (WM) is an incurable B-cell lymphoproliferative disorder characterized by a rising incidence, particularly among older adults. Despite its growing prevalence, mortality trends remain poorly characterized. This study evaluates WM mortality trends and demographic disparities in the United States from 1999 to 2020. Methods: Age-adjusted mortality rates (AAMR) per 100,000 individuals for WM (ICD-10: C88.0) were obtained from CDC WONDER. Annual percentage changes (APC) and 95% confidence intervals were estimated using permutation tests, and the average annual percentage change (AAPC) was calculated as a weighted average. Joinpoint regression was used to assess trends over time. Results: From 1999 to 2020, 11,359 WM-related deaths were recorded, with an overall AAMR of 0.45 (95% CI: 0.44–0.45). The AAMR declined significantly from 1999 to 2015 (APC: -4.01, 95% CI: -4.66 to -3.36) before rising sharply from 2015 to 2020 (APC: 7.18, 95% CI: 2.73 to 11.83). Males had a higher AAMR of 0.66 (95% CI: 0.64–0.68) compared to 0.30 (95% CI: 0.30–0.31) for females, with both sexes showing an upward trend in mortality post-2015. Regional analysis revealed that the West and Midwest had the highest AAMRs at 0.50 (95% CI: 0.48–0.52), with a particularly marked increase in the West after 2017. The South recorded the lowest AAMR at 0.32 (95% CI: 0.31–0.33). Top 10th percentile states, including Maine, Minnesota, New Hampshire, and Vermont, had the highest AAMRs (> 0.70), while bottom 10th percentile states, such as Alabama, Arkansas, Georgia, Louisiana, and Mississippi, showed the lowest AAMRs (≤ 0.27). Urban areas exhibited slightly higher AAMRs (0.45, 95% CI: 0.44–0.46) than rural areas (0.41, 95% CI: 0.39–0.42). Most deaths occurred among individuals aged 75 and older, with the highest proportion in medical facilities (38.6%), followed by deaths at home. Conclusions: Despite an initial decline, WM mortality has risen significantly since 2015, particularly among males and in the Western U.S. These findings suggest potential shifts in disease biology, treatment resistance, or disparities in care. Limitations of CDC WONDER, including potential ICD code misclassification, may affect data accuracy. Further research is needed to elucidate the drivers of these trends and optimize therapeutic strategies for high-risk populations, particularly older adults and males.