Social determinants of health and long-term survival in chronic lymphocytic leukemia/small lymphocytic lymphoma: A population-based analysis of 118,667 patients

Abstract Background: Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) exhibits heterogeneous outcomes influenced by biological and socioeconomic factors. While therapeutic advances have improved survival, the impact of social determinants on long-term outcomes remains incompletely characterized. We conducted one of the largest population-based analysis examining socioeconomic disparities in CLL/SLL survival across two decades. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 119,950 patients diagnosed with CLL/SLL between 2000-2022. After excluding 1,283 cases identified through death certificate or autopsy only, 118,667 patients comprised the analytic cohort. County-level median household income served as a proxy for socioeconomic status (SES), categorized into quartiles: Very High (>$100k), High ($80-100k), Medium ($60-80k), and Low (<$60k). Primary endpoint was overall survival (OS). Kaplan-Meier methods estimated survival probabilities at multiple timepoints. Cox proportional hazards models evaluated independent prognostic factors. Results: The cohort included 71,146 (60.0%) males and 47,521 (40.0%) females with median age 72 years. Geographic distribution comprised 67,728 (57.1%) from large metropolitan areas. Among 110,425 patients with available income data, distribution was: Very High 19,962 (18.1%), High 34,846 (31.6%), Medium 40,215 (36.4%), and Low 15,402 (13.9%). Overall 5-year OS was 68.0%, with 1-year 89.9%, 3-year 78.5%, and 10-year 46.1%. Median survival was 11.5 years. Significant survival disparities emerged across all income levels (p<0.001). Five-year OS ranged from 70.6% (Very High) to 62.7% (Low), representing 7.9% absolute difference. This gap progressively widened: 2.9% at 1-year (90.8% vs 87.9%), 5.8% at 3-years (80.4% vs 74.6%), and 10.5% at 10-years (49.7% vs 39.2%), with P-value all <001. Temporal analysis revealed persistent disparities. Among patients diagnosed 2000-2009, 5-year OS was 67.5% (Very High) versus 59.4% (Low), difference 8.1%. For 2010-2014: 73.3% versus 64.9%, difference 8.4%. For 2015-2019: 73.4% versus 65.0%, difference 8.4%. Thus, while absolute survival improved (2000-2009: 64.7%; 2010-2014: 70.3%; 2015-2019: 71.0%), income-based disparities remained unchanged. Age demonstrated the strongest prognostic impact. Five-year OS by age: 20-39 years 89.4%, 40-59 88.0%, 60-69 81.0%, 70-79 66.3%, ≥80 35.8% (p<0.001). Ten-year OS showed dramatic differences: 82.3% (20-39) versus 10.8% (≥80). Sex-based disparities persisted with female 5-year OS 70.4% versus male 66.5% (p<0.001). Geographic location influenced outcomes: large metropolitan 69.0% versus other areas 66.7% (p<0.001). Marital status significantly impacted survival: married 72.3%, single 67.8%, divorced/separated 68.7%, widowed 47.8% (p<0.001). Multivariable Cox regression confirmed independent prognostic significance. Age remained dominant (HR=1.83 per decade). Compared to highest income, mortality risk progressively increased: High HR=1.10, Medium HR=1.21, Low HR=1.38 (all p<0.001). Male sex (HR=1.22), non-metropolitan residence (HR=1.09), and widowed status (HR=1.45) independently predicted inferior survival. Recent diagnoses showed dramatic improvement: 2020-2022 HR=0.09 versus 2000-2009. Conclusions: This comprehensive analysis of 118,667 CLL/SLL patients demonstrates persistent socioeconomic disparities despite therapeutic advances. Low-income patients experience 38% higher mortality risk, with survival gaps widening over time. While recent diagnostic periods show remarkable improvements, these gains have not eliminated socioeconomic inequities. These findings underscore the critical need for interventions addressing healthcare access barriers and social determinants to achieve equitable outcomes in CLL/SLL.