Introduction: Chronic myeloid leukemia (CML) is a clonal stem cell malignancy defined by the BCR::ABL1 fusion. Although outcomes in clinical trials have improved dramatically with the advent of tyrosine kinase inhibitors (TKIs), the extent to which these gains have translated into population-level survival improvement needs periodic assessment. The age-adjusted mortality-to-incidence ratio (AAMIR) offers a pragmatic metric to assess survival trends across varied demographic and geographic contexts.

Methods: We accessed the CDC WONDER United States Cancer Statistics database for CML incidence and mortality data (1999–2021) for adults ≥20 years, stratified by year, age (20–39, 40–65, ≥65 years), gender, race/ethnicity (Non-Hispanic Whites [NHW], Non-Hispanic Blacks [NHB], Hispanics [HSP], Non-Hispanic American Natives [NHAN], Non-Hispanic Asian/Pacific Islanders [NHAPI]), region, and state. Age-Adjusted Incidence Rates (AAIR) and Age-Adjusted Mortality Rates (AAMR) per 100,000 were standardized to the 2000 U.S. Census, with AAMIR) calculated annually (AAMR/AAIR) using STATA. Joinpoint Regression assessed trends, reporting Annual Percentage Change (APC) and Average Annual Percentage Change (AAPC).

Results: Between 1999 and 2021, there were 135,646 CML cases and 27,313 CML-related deaths. The overall AAIR increased from 2.19 to 2.64 (AAPC: 0.75%, p=0.04), while AAMR declined from 0.90 to 0.41 (AAPC: –3.61%, p<0.01). The AAMIR dropped from 0.411 to 0.156 (AAPC: –4.33%, p<0.01), reflecting marked survival gains over time. The AAMIR declined steeply from 1999-2005 (APC: -10.68%, p<0.001), continued to decline at a slower rate from 2005-2013 (APC: -4.64%, p<0.001) and increased slightly (APC: +1.05%, p=0.02) from 2013-2021. Bot males and females exhibited significant AAMIR reductions (males: 0.404–0.168; AAPC: –4.09%, p<0.01; females: 0.420–0.146; AAPC: –4.68%, p<0.01) overtime. Age influenced AAMIR significantly, with young adults (20–39y) achieving the greatest improvement (0.376–0.052; AAPC: –8.61%, p<0.01) followed by middle-aged adults (40–64y) (0.381–0.077; AAPC: –6.16%, p<0.01) and older adults (≥65y) (0.436–0.238; AAPC: –2.92%, p<0.01). For older adults, the rate of decline slowed down, with a slight increase in AAMIR from .210 in 2013 to .237 in 2021 (APC: +1.13%, p = 0.02). All racial and ethnic groups showed substantial improvements over time; NHB (0.443–0.146; AAPC: –4.23%, p<0.01), NHW (0.411–0.158; AAPC: –4.23%, p<0.01), HSP (0.410–0.141; AAPC: –4.77%, p<0.01), and NHAPI (0.322–0.127; AAPC: –4.28%, p<0.01).

Regionally, the South had the highest burden, with rising AAIRs (2.08–2.78; AAPC: 1.26%, p<0.01), though AAMIR fell from 0.420 to 0.159 (AAPC: –4.25%, p<0.01). The Northeast maintained the lowest AAMIRs (0.406–0.109; AAPC: –5.00%, p<0.01). The Midwest and West showed similar declines (Midwest: 0.418–0.163; AAPC: –3.83%, p<0.01; West: 0.391–0.187; AAPC: –3.72%, p<0.01). State-level analysis revealed geographic variation in AAMIR trends. New York had the greatest AAMIR reduction (0.422–0.114; AAPC: –6.03%, p<0.01), followed by North Carolina (0.462–0.132; AAPC: –6.38%, p<0.01) and New Jersey (0.398–0.099; AAPC: –5.74%, p<0.01). In contrast, Arizona showed limited progress (0.338–0.208; AAPC: –2.43%, p=0.065), with a post-2017 AAMIR rise. California (0.386–0.178; AAPC: –3.66%, p<0.01) and Pennsylvania (0.425–0.099; AAPC: –4.06%, p<0.01) had slower declines, underscoring regional variations in CML outcomes.

Conclusions: This national analysis demonstrates substantial improvements in CML survival over time, with marked declines in AAMIRs across all demographic groups, likely driven by advances in TKI therapies. However, disparities by age and geography persist; outcomes in older adults improved initially but saw a modest decline in more recent years, perhaps highlighting an interaction between advance age and TKI toxicity. Geographic variations in outcomes also point to an opportunity to address access to care and social determinants of health when comparing healthcare systems and therapeutic approaches.

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2025
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