Persistent racial disparities in Sézary syndrome outcomes despite use of modern therapies: A single-center analysis

Abstract

Abstract Introduction Sézary syndrome (SS) is a rare and aggressive leukemic variant of cutaneous T-cell lymphoma. Historically, Black patients with SS have faced disproportionately poorer outcomes, though the basis for this disparity is unclear, whether due to access to care, biological, or therapeutic factors. With the increasing use of modern systemic therapies (e.g., mogamulizumab, brentuximab vedotin, interferons, photopheresis) over the past decade, we sought to determine whether survival disparities by race persist in the current treatment era. Methods We retrospectively reviewed 75 patients with SS treated between January 2015 and June 2025 at Moffitt Cancer Center. SS diagnosis was confirmed by the presence of both B2 blood involvement (tumor burden >1000/μL) and erythroderma, or B1 disease with blood involvement close to 1000/μL and erythroderma. Patient demographics, disease characteristics, and treatment data were collected. Race was self-reported as White, Black, or Other. Overall survival (OS) was measured from the time of confirmed B2 transformation to death or last follow-up and estimated using the Kaplan–Meier method. Cox proportional hazards modeling was used to assess associations between race and OS, adjusting for potential confounders including age, sex, SS subtype (primary vs. secondary), stage at diagnosis, visceral involvement, and large-cell transformation (LCT). Results Seventy-five patients were confirmed to have SS; among them, 56 (75%) were White, 13 (17%) were Black, and 6 (8%) were of Other or mixed race. The median age at diagnosis was 73 years (range: 29–92). A higher proportion of Black patients were diagnosed before age 60 compared to White patients (38.5% vs. 10.7%, p = 0.041), had stage IVB disease (30.8% vs. 8.9%, p = 0.047), and had a significantly higher frequency of LCT (76.9% vs. 30.4%, p = 0.003). Sex distribution did not differ significantly between groups (p = 0.83). At a median follow-up of 57 months, the cohort's median OS had not yet been reached (95% CI: 48.8 months–Not Reached). Estimated OS was 87.8% (95% CI, 80.7–95.6) at 12 months and 72.1% (95% CI, 61.7–84.3) at 36 months. Racial stratification revealed a marked survival gap: 1-year OS was 76.2% (95% CI, 55.8–100) in Black patients versus 89.1% (95% CI, 81.3–97.7) in White patients; 3-year OS was 35.5% (95% CI, 15.1–83.5) versus 82.2% (95% CI, 72.2–93.6), respectively. In univariate analysis, Black race was associated with significantly worse OS compared with White race (HR = 3.6; 95% CI, 1.56–8.33; p = 0.007). LCT also predicted worse outcomes (HR = 2.13; 95% CI, 1.01–4.48; p = 0.047). In multivariate analysis adjusting for age, sex, LCT, and SS subtype, Black race remained an independent adverse factor (HR = 3.1; 95% CI, 1.22–7.69; p = 0.018). Other covariates were not significantly associated with survival. When examining treatment patterns across racial groups, extracorporeal photopheresis (ECP) remained the backbone for both Black and White patients (77% vs. 86%). The most common reasons for ECP not being used were poor intravenous access and travel burden. Mogamulizumab was used at similar rates in both groups (75% in Black patients vs. 69.2% in White patients). Black patients were more likely to receive ECP + Pegasys (69.2% vs. 26.8%), romidepsin (61.5% vs. 37.5%), brentuximab (38.5% vs. 14.3%), and combination chemotherapy (61.5% vs. 19.6%) compared to White patients, likely reflecting the more aggressive nature of their disease. ConclusionOur cohort demonstrated better OS compared to historical studies, likely reflecting the impact of modern systemic therapies and specialized care at a tertiary center. However, despite broader access to ECP and novel agents such as mogamulizumab and brentuximab, the survival gap between Black and White patients remained consistent with prior population-based reports. The disparity persisted even after adjusting for disease aggressiveness and clinical covariates, suggesting that treatment alone does not fully mitigate the survival gap. Black patients in our cohort had a markedly higher prevalence of large-cell transformation, earlier age at diagnosis, and more advanced clinical stage at presentation, suggesting possible biological differences. These findings underscore the urgent need to better understand the intersection of race, tumor biology, and treatment response in SS and to develop tailored strategies that ensure equitable outcomes across all racial groups.