Effects of antibiotic use on survival and immune-related adverse events among patients with cutaneous malignancies receiving an immune checkpoint inhibitor

Summary: Abstract Body: The advancement of immune checkpoint inhibitors (ICI) has drastically improved the prognosis of cutaneous malignancies. Nevertheless, despite an average objective response rate to ICIs ranging from 33% to 68%, many patients continue to exhibit a limited or no response. While several retrospective cohort studies have suggested antibiotic (Abx) use as a potential culprit for the variable outcome by disrupting the gut microbiome and subsequently impairing the ICI-mediated antitumor immunity, results have been conflicting. We leveraged a large international deidentified electronic health record database to investigate whether Abx use (e.g., Penicillins, Quinolones, Cephalosporins, and Carbapenems) up to 3 months prior to initiating a single ICI agent would alter survival outcomes among patients with Metastatic Melanoma (MM) or Merkel Cell Carcinoma (MCC). Cohorts were 1:1 propensity matched for covariables of age, sex, ethnicity, smoking status, sites of metastases, and several comorbidities. MM patients who received Abx prior to a PD-1 inhibitor (n=3362) had lower survival at 1 month (96.3% vs 97.3%, log-rank test=0.023) and 3 months (91.9% vs 92.7%, 0.228), but significantly higher survival by 5 years (61.0% vs 56.8%, 0.033). Similar trends were observed for MCC patients who received Abx prior to either a PD-1 or PD-L1 inhibitor (n=113) at 1 month (90.9% vs 93.8%, 0.415) and 3 months (77.2% vs 92.4%, 0.005), with higher, albeit not significant, survival at 5 years (62.6% vs 39.6%, 0.329). Abx use was also associated with a lower hazard ratio for common immune-related adverse events (e.g., Enteritis and Colitis) among MM patients (0.85, 95% CI 0.76-0.99), whereas MCC patients had comparable outcomes. Results of this study highlight the potential temporal impact of Abx usage prior to initiating ICI therapy among patients with certain cutaneous malignancies, potentially eliciting long-term survival benefit. Jacky H. Chen¹, Alan Shen¹, Alan Gordillo¹, Joshua Arbesman² 1. Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, United States. 2. Department of Dermatology, Cleveland Clinic, Cleveland, OH, United States. Pigmentation, Melanoma, and Melanoma Immune Surveillance