Trends and disparities in mortality from chronic lymphocytic leukemia in the geriatric population in the United States from 1999 to 2020: A nationwide analysis

Abstract Background: Chronic Lymphocytic Leukemia (CLL) is the most prevalent leukemia among adults in Western populations, disproportionately affecting the elderly, with a median age at diagnosis of approximately 70 years. Over the past two decades, significant advancements in therapeutic options, including Bruton tyrosine kinase (BTK) inhibitors, BCL-2 antagonists, and monoclonal antibodies, have improved clinical outcomes. However, despite these advances, limited data exist on long-term mortality trends and disparities in CLL outcomes among older adults in the United States. Understanding such patterns is critical to guiding geriatric oncology care, identifying gaps in healthcare delivery, and informing public health strategies. Methods: We conducted a population-based analysis using the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) Underlying Cause-of-Death database. We identified all deaths among individuals aged ≥65 years from 1999 to 2020 in which CLL (ICD-10 code C91.1) was listed as the underlying cause. Mortality data were stratified by sex, age group (65–74, 75–84, ≥85), U.S. Census region, urban-rural classification, state, and place of death. We calculated crude mortality rates (CMRs) and age-adjusted mortality rates (AAMRs) per 100,000 persons, standardized to the U.S. 2000 population. Joinpoint regression analysis was used to assess temporal trends in AAMRs and compute annual percent changes (APCs) and average annual percent changes (AAPCs), with statistical significance set at p<0.05. Results: Between 1999 and 2020, a total of 85,371 CLL-related deaths occurred among U.S. adults aged ≥65 years. The overall AAMR declined from 11.18 per 100,000 in 1999 to 7.75 in 2020, reflecting a significant downward trend (AAPC: -1.86%; 95% CI: -2.18 to -1.54; p<0.0001). Men consistently exhibited higher mortality rates (AAMR: 13.48) than women (AAMR: 6.45), though the mortality decline was more pronounced among women (AAPC: -2.10% vs. -1.65%, respectively; both p<0.0001). Regional disparities were evident, with the Midwest reporting the highest AAMR (10.63), and the West the lowest (8.71). Urbanization analysis revealed higher mortality in non-metropolitan areas (AAMR: 10.33) than metropolitan ones (AAMR: 9.08), though both experienced significant declines over time. Age-stratified analysis showed the steepest declines in the 65–74 age group (AAPC: -3.91%; p<0.0001), followed by those aged 75–84 years (AAPC: -1.96%) and ≥85 years (AAPC: -0.25%). States with the highest mortality included Minnesota, Iowa, and South Dakota, while Hawaii, Nevada, and New Mexico had the lowest. Most deaths occurred in medical facilities (43.8%), followed by home (26.7%), nursing homes/long-term care (19.5%), and hospice (5.6%). Conclusion: CLL-related mortality among the U.S. geriatric population declined significantly between 1999 and 2020, likely reflecting the impact of therapeutic innovations and improved disease management. However, substantial disparities persist across sex, age, region, urbanization, and state-level subgroups. These findings underscore the importance of equitable access to modern CLL treatments and the need for targeted interventions to reduce mortality in high-risk, underserved older populations. Efforts to close these gaps will be essential in optimizing outcomes in the era of personalized cancer care for aging Americans.