Clinical and socioeconomic prognostic factors in chronic lymphocytic leukemia with normal FISH.

Abstract

e19025 Background: Chronic lymphocytic leukemia (CLL) is the most common leukemia, with an estimated 23,690 new cases in 2025. Fluorescent in situ hybridization (FISH) provides important prognostic information and is routinely incorporated alongside the Rai staging systems to guide risk stratification and treatment decisions. Approximately 20% of patients with CLL have normal FISH results. Outcomes in this subgroup remain heterogeneous, and data are limited regarding the clinical, cytogenetic, and socioeconomic factors that may influence prognosis, including the potential impact of underlying karyotypic complexity not captured by standard FISH panels. Herein, we aim to evaluate clinical and socioeconomic prognostic factors associated with outcomes in patients with CLL who have normal FISH results. Methods: This is a single center retrospective study which included patients over 18 years of age with a diagnosis of CLL and a normal standard FISH panel. Primary end points were time to treatment initiation (TTI) and overall survival (OS). Descriptive statistics were used to summarize baseline characteristics. Time-to-event outcomes (TTI and OS) were estimated using Kaplan–Meier methods. Overall survival was summarized by reporting 5-year survival rates. Univariate and multivariate Cox regression models were used to analyze predictors of TTI and OS. Results: We identified 163 patients with CLL and normal FISH results between 2007-2025. Median age was 66.2 years, 82 were male (50.3%) and majority were non-Hispanic whites (89%), had Medicare insurance (66.2%) and were IgHV mutated (66.2%). With a median follow up of 65 months, the median TTI was 32 months, and 5-year OS was 92.1%. On multivariable analysis, older age (HR 1.06, 95 % CI 1.03-1.08, p<0.001), commercial insurance (HR 3.23, 95% CI 1.91-5.50, p <0.001), Medicaid (HR 5.58 95% CI 1.90-16.39, p < 0.002), Other/non-insured (HR 3.86, 95% CI 2.11-7.05, p<0.001) were associated with decreased survival. While older age (HR 1.04, 95% CI 1.02-1.06, p<0.0001), commercial insurance (HR 2.2, 95% CI 1.32-3.68, p=0.0025), Medicaid (HR 4.36, 95% CI 1.52-12.52, p=0.0063) and other/uninsured (HR 2.11, 95% CI 1.17-3.82, p=0.0137) were associated with shorter time to treatment initiation. IgHV status did not affect survival (HR 1.08, CI 0.76-1.52, p=0.67) or TTI (HR 0.93, 95% CI 0.66-1.31, p=0.67). Conclusions: In CLL patients with normal FISH, age and insurance status were significantly associated with survival and time to treatment initiation, highlighting the importance of demographic and socioeconomic determinants of outcome. In contrast, IgHV status did not demonstrate prognostic significance in this subgroup in our cohort.