Relationship between immune-mediated adverse events and clinical outcomes in patients with metastatic melanoma treated with immune checkpoint inhibitors (ICIs): A retrospective real-world analysis.

Abstract

11144 Background: ICIs targeting programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) revolutionized the treatment landscape for advanced melanoma. However, these agents can cause immune-related adverse events (AEs). Several studies have demonstrated a correlation between AEs and improved clinical outcomes. Understanding the co-occurrence patterns and prognostic implications of immune-related adverse events, as well as the impact of concomitant medications such as antibiotics (ATB), immunosuppressants (IS) and/or corticosteroids (CS), and proton pump inhibitors (PPIs), is crucial for immunotherapy management. In this study, we evaluated the relationship between immune-related toxicity, the use of IS and/or CS and ATB, and progression-free survival (PFS) and overall survival (OS) in patients with advanced melanoma treated with ICIs. Methods: Retrospective, analytical, multicenter study of patients (pts) with stage IV melanoma treated with ICIs (ipilimumab/nivolumab, nivolumab or pembrolizumab), between 2014 and 2025. Immune-related adverse events were graded according to CTCAE criteria and categorized as none, grade 1-2 or 3-4, demographic characteristics, use of IS and/or CS, ATB and number of toxicities were obtained from medical records. PFS and OS were estimated using the Kaplan-Meier method and compared using Cox proportional hazards models, with statistical significance set at p < 0.05. Results: Among 364 pts included, 275 (77,4%) experienced AEs. Dermatologic end endocrine toxicities, including rash, pruritus, vitiligo, hypothyroidism and hypophysitis were associated with improved survival outcomes. The results regarding PFS in relation to the presence, grade, and number of toxicities, as well as the use of IS and/or CS and ATB, are described in the table below. OS showed a statistically significant association with toxicity grade, with better OS observed among patients with grade 1–2 toxicity (HR 0.55; 95% CI, 0.35-0.87; P = 0.010), as well as who did not use IS and/or CS (HR 1.84; 95% CI, 1.20-2.82; P = 0,005). PFS showed a trend toward improved outcomes in patients who did not use PPI, without statistical significance due to the small number of pts. Conclusions: Our data show that pts who developed grade 1–2 toxicity and did not receive IS and/or CS experienced improved OS and PFS when treated with ICIs. Pts with a greater number of different toxicities and those who did not use ATB experienced better PFS. Parameter HR for PFS 95% CI p-value Toxicity vs. No Toxicity 0.39 0.29-0.52 <0.001 Degree of toxicity 0 vs. Grade 1+2 0.38 0.28-0.51 <0.001 0 vs. Grade 3+4 0.50 0.35-0.73 <0.001 Number of toxicities 0 vs. 1-2 0.50 0.38-0.67 <0.001 0 vs. 3 or + 0.26 0.17-0.38 <0.001 IS and/or CS vs. No IS and/or CS 1.43 1.05-1.95 <0.022 ATB vs. No ATB 1.53 1.11-2.12 <0.010