Impact of alcohol dependence on the efficacy of immune checkpoint inhibitors: A comprehensive real-world retrospective cohort analysis.

Abstract

e23091 Background: Immune checkpoint inhibitors (ICIs) are pivotal in treating various cancers by targeting PD-1 and PD-L1. Alcohol consumption has been associated with modifying PD-1/PD-L1 activity, which may influence the efficacy of ICIs. A prior study in murine models demonstrated that ethanol exposure may upregulate the PD-1/PD-L1 pathway and inhibit T cell anti-tumor function. Another study in mouse models, demonstrated that alcohol induces expression of aldehyde dehydrogenase 2 which stabilizes PD-L1 expression in colon cancer cells, leading to immune escape. The purpose of this large multicenter cohort study is to evaluate the effect of alcohol dependence history on ICI therapy outcomes. Methods: We utilized the TriNetX Network, a database comprising over 130 million deidentified patient records, to assess the impact of immune checkpoint inhibitor (ICI) therapy on mortality outcomes in patients with and without a history of alcohol dependence (ICD10: F10.20) across multiple cancer types. To ensure comparability, 1:1 propensity-score matching was conducted, accounting for demographics, laboratory values, and relevant comorbidities across each cancer type. Results: A total of 82,635 cancer patients who underwent ICI therapy for treatment of lung, breast, melanoma, colorectal, head and neck, bladder, hepatocellular, and renal cell carcinoma were identified, of whom 3.71% had a diagnosis of alcohol dependence. After propensity score matching individually in each cancer type, 3,002 patients were in the alcohol group and 3,002 were in the non-alcohol group. For each cancer type investigated, there was no statistically significant difference in survivability based on Kaplan-Meier analysis (Table 1). Conclusions: This study suggests that though there may be a theoretical influence of alcohol on the efficacy of ICI therapy at the molecular level, clinically, alcohol dependence does not significantly impact morality in patients treated with ICI therapy across cancer types. Survivability in patients with a diagnosis of alcohol dependence compared to non-alcohol dependence treated with ICIs across cancer types. Cancer type (ICD 10) N (Alcohol Dependence) N (Non-Alcohol Dependence) 3-year HR 95% CI Colon (C18) 39 39 0.584 (0.258,1.323) Liver (C22.0) 135 135 0.722 (0.498,1.045) Lung (C34) 72 72 0.96 (0.535,1.723) Breast (C50) 389 389 0.987 (0.809,1.205) Bladder (C67) 282 282 1.007 (0.737,1.375) Renal cell (C64) 1,766 1,766 1.048 (0.954,1.15) Head & neck (C76.0) 204 204 1.09 (0.84,1.415) Melanoma (C43) 115 115 1.312 (0.885,1.945)