Impact of neighborhood socioeconomic deprivation and diet quality on immune checkpoint blockade outcomes.

Abstract

1545 Background: Immune checkpoint blockade (ICB) has significantly improved survival across multiple advanced malignancies; however, outcomes remain heterogeneous. While socioeconomic disadvantage (SED) is known to adversely affect cancer outcomes through delayed diagnosis and access to care, impact of SEDupon ICB efficacy remains incompletely characterized. The Area Deprivation Index (ADI) is a validated, neighborhood-level measure of SED. We evaluated the association between ADI and clinical outcomes to ICB across a large, multi-state integrated cancer network. Methods: We identified 1,699 adult patients with advanced cutaneous melanoma (CM), renal cell carcinoma (RCC), or urothelial carcinoma (UC) treated with first-line ICB (monotherapy or combination) between 2013–2025 within the UPMC Hillman Cancer Center network (>70 sites across four states). ADI scores were derived from 9-digit ZIP codes at ICB initiation using the Neighborhood Atlas and categorized into quartiles, with higher quartiles indicating greater SED. Primary endpoints were time-to-next therapy (TTNT) and overall survival (OS), measured from ICB initiation to initiation of subsequent systemic therapy or death, respectively. Outcomes were analyzed by ADI quartile using Kaplan–Meier methods and Cox proportional hazards models adjusted for relevant clinical covariates. Analyses were limited to first ICB exposure. Results: Across 2,156.3 person-years follow-up, patients in highest ADI quartile experienced a significantly higher incidence of TTNT events compared with lowest quartile (31.1% vs 22.8%; χ² p=0.008), without a corresponding increase in deaths (39.2% vs 38.4%; χ² p=0.86). Highest ADI status was independently associated with inferior TTNT after first-line ICB in CM (HR 1.51; 95% CI 1.01–2.27; p=0.04), RCC (HR 1.58; 95% CI 1.02–2.45; p=0.04), and UC (HR 2.02; 95% CI 1.11–3.68; p=0.01). Association between ADI status and OS were not statistically significant after adjustment for confounding variables. Univariate and multivariate analyses were performed to control for confounding variables, and confirmed independent prognostic impact of highest ADI quartile upon inferior TTNT. Within a subset of ICB-treated CM patients with available dietary intake data, highest ADI quartile had lowest Healthy Eating Index (HEI) scores (Wilcoxon p=0.01). Conclusions: Neighborhood-level SED is associated with inferior durability of response to first-line ICB across multiple solid tumors. These findings suggest that SED may influence ICB effectiveness beyond treatment access alone and underscore the need to identify biologic and care-delivery mechanisms—potentially including diet, comorbidities, and the gut microbiome—through which deprivation impacts ICB outcomes. Prospective, pan-cancer studies integrating social, clinical, and biological variables are warranted.