Survival outcomes in individuals with cancer and pre-existing autoimmune disease receiving immune checkpoint inhibitors: A multicenter, propensity-matched real-world survival analysis.

Abstract

11098 Background: Autoimmune disease (AID) affects approximately 5–10% of individuals with cancer. Although immune checkpoint inhibitors (ICIs) have transformed cancer therapy, individuals with pre-existing AID are routinely excluded from clinical trials due to concerns about immune-related adverse events. Consequently, long-term real-world survival outcomes in this population remain incompletely defined, limiting evidence-based risk–benefit assessment. Methods: We conducted a retrospective, multicenter cohort study using a large U.S.-based real-world oncology network derived from harmonized electronic health records across academic and community cancer centers. Adults (≥18 years) with solid tumors who received at least one immune checkpoint inhibitor (PD-1, PD-L1, or CTLA-4) were included. Individuals were classified by the presence or absence of documented pre-existing AID prior to ICI initiation. Cohorts were matched 1:1 using propensity scores based on age, sex, race, and baseline comorbidities, including cardiovascular disease, diabetes, chronic kidney disease, chronic obstructive pulmonary disease, cerebrovascular disease, and heart failure. Survival outcomes at 1, 3, and 5 years from ICI initiation were evaluated using Kaplan–Meier methods and Cox proportional hazards models. Results: After propensity score matching, 13,800 adults were included (6,900 with AID and 6,900 without), with excellent balance across baseline covariates. All-cause mortality was higher among individuals with pre-existing AID at 1 year (36.7% vs 32.6%), 3 years (48.3% vs 44.7%), and 5 years (50.1% vs 47.0%). Pre-existing AID was independently associated with worse overall survival at all time points (HR 1.15; 95% CI 1.09–1.22 at 1 year; HR 1.15; 95% CI 1.10–1.21 at 3 years; HR 1.15; 95% CI 1.09–1.20 at 5 years; all P < 0.001). Kaplan–Meier analyses demonstrated early separation of survival curves that persisted through long-term follow-up (log-rank P < 0.001). Conclusions: In this large, multicenter, real-world cohort, pre-existing autoimmune disease was associated with a modest but durable reduction in survival among individuals treated with immune checkpoint inhibitors, persisting through 5 years of follow-up. These findings do not contraindicate ICI use but highlight the need for individualized risk stratification, multidisciplinary collaboration, proactive toxicity surveillance, and informed shared decision-making when initiating immunotherapy in this population.