Abstract Introduction: Chronic lymphocytic leukemia (CLL) is the most prevalent form of leukemia among older adults, with mortality trends influenced by advances in diagnostics and therapeutics over recent decades. However, a comprehensive long-term evaluation of CLL mortality in the elderly U.S. population remains limited. This study assesses nationwide trends in CLL-related mortality among adults aged ≥65 from 1968 to 2023 across various demographic and geographical variables. Methods: Data on CLL-related deaths were obtained from the CDC WONDER database (1968–2023), identifying deaths where CLL was listed as the underlying cause using ICD-8/9 code 204.1 and ICD-10 code C91.1. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated for individuals aged ≥65 using the 2000 U.S. standard population. Joinpoint regression was used to estimate annual percent changes (APCs) and average annual percent changes (AAPCs). The stratification was done on the basis of gender, ethnicity/race, age groups (65–74, 75–84, ≥85 years), and census regions. Results: From 1968 to 2023, there were 175,856 CLL-related deaths among U.S. adults aged ≥65. The mean AAMR was 9.3 per 100,000 in 1968, peaking at 11.4 in 1996 and declining to 7.4 in 2023. Joinpoint regression identified four segments: mortality significantly increased from 1968–1999 (APC: +0.71%, 95% CI: 0.6 to 0.9, p0.001), followed by a significant decline from 1999–2013 (APC: −1.32%, 95% CI: −1.7 to −0.9, p0.001). Non-significant declines occurred from 2013–2016 (APC: −4.58%, 95% CI: −10.3 to 1.5, p=0.13) and 2016–2023 (APC: −0.71%, 95% CI: −1.59 to 0.18, p=0.11). The overall average annual percent change (AAPC) from 1968 to 2023 was −0.29% (95% CI: −0.7 to 0.08, p=0.13), indicating a long-term but statistically non-significant decline. The overall AAMR was higher in males (14.1 per 100,000) than females (6.7 per 100,000). In females, mortality significantly declined (AAPC: -0.40%; 95% CI: -0.55 to -0.25; p 0.00001), with a shift from an increase (1968–1999: APC: +0.84%, p 0.0001) to a decline (1999–2023: APC: -1.98%; 95% CI: -2.21 to -1.76; p 0.0001). Overall male mortality plateaued non-significantly (AAPC: -0.25%; 95% CI: -0.65 to 0.15; p = 0.215), increasing from 1968 to 1996 (APC: +0.87%, p 0.0001), then declining from 1996 to 2012 (APC: -1.03%, p 0.001). A sharper but non-significant decline occurred between 2012 and 2016 (APC: -4.48%, p = 0.070), followed by stabilization through 2016–2023 (APC: -0.46%, p = 0.353). Racially, AAMR was higher among White compared to Black or African American individuals (9.96 vs. 8.06 per 100,000). Among Black or African Americans, mortality rose significantly from 1968–1991 (APC +2.24%, 95% CI 1.70–2.78, p 0.0001), then declined from 1991–2006 (APC -0.88%, 95% CI -1.70 to -0.05, p = 0.038), followed by a sharper decrease from 2006–2023 (APC -3.08%, 95% CI -3.64 to -2.51, p 0.0001). Whites showed no significant change until 2001, after which mortality declined significantly through 2023 (APC -1.51%, 95% CI -1.69 to -1.32, p 0.0001). Overall average annual percent changes were nonsignificant for both races. The crude mortality rate was lowest in adults aged 65–74 years (4.8 per 100,000), more than doubled in those aged 75–84 years (11.6 per 100,000), and was highest in the ≥85 age group (27 per 100,000).Regionally,the Midwest had the highest overall AAMR (10.87), followed by the South (9.28), Northeast (9.21), and West (9.01). Significant long-term declines were observed in the Northeast (AAPC: –0.36%; 95% CI: –0.60 to –0.11; p = 0.005), South (–0.33%; 95% CI: –0.60 to –0.07; p = 0.015), and West (–0.33%; 95% CI: –0.51 to –0.15; p 0.001). The Midwest showed a non-significant overall decline (AAPC: –0.40%; 95% CI: –1.00 to +0.20; p = 0.189). Conclusion: Over the past five decades, CLL-related mortality among U.S. adults aged ≥65 initially rose but has significantly declined since the late 1990s, reflecting advancements in diagnosis and treatment. Despite these gains, disparities persist by sex, age, race, and region. Males, older age groups, and residents of the Midwest continue to bear a higher mortality burden. The overall decline was statistically significant in females. Whereas Black individuals have experienced the recent improvements, overall long-term declines remain statistically modest. Continued efforts are needed to sustain and enhance mortality reduction, particularly in high-burden subpopulations.
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