Relationship between immune-mediated adverse events and clinical outcomes in patients with metastatic melanoma treated with immune checkpoint inhibitors (ICI): A single institution experience.

Abstract

e21531 Background: ICI targeting programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) revolutionized the treatment scenario for advanced melanoma. However, these agents can cause immune-related adverse events (AEs) ranging from mild to severe. Various studies demonstrated a correlation between the occurrence of AEs and better clinical outcomes. Understanding co-occurrence patterns and prognostic implications of immune-related adverse events is crucial for immunotherapy management. In this study, we evaluated the relationship between immune-related toxicity and progression-free survival (PFS) and overall survival (OS) in patients with advanced melanoma treated with ICI. Methods: Retrospective and analytical study of patients (pts) with stage IV melanoma treated with ICIs (ipilimumab/nivolumab, nivolumab or pembrolizumab), between 2014 and 2024 at a single institution. Demographic characteristics, types of AEs, categorization of grades into 0, 1+2 and 3+4 using the CTCAE criteria and number of toxicities were obtained from medical records. PFS and OS were estimated using the Kaplan-Meier method, with statistical significance set at p < 0.05. Results: A total of 272 pts were included in the study. 201 (75.6%) pts experienced AEs. The most common were pruritus (42.3%), rash (41.8%), colitis (34.8%), vitiligo (15.4%), hypothyroidism (14.4%) and hypophysitis (13,4%). The PFS in relation to the presence of toxicity versus no toxicity was statistically significant (HR 0.37; 95% CI 0.27-0.51; p < 0.001). There was also a statistically significant correlation between certain toxicities and PFS: vitiligo (HR 0.38; 95% CI 0.22-0.67; p < 0.001), rash (HR 0.64; 95% CI 0.46-0.88; p = 0.007), pruritus (HR 0.65; 95% CI 0.47-0.89; p = 0.008) and hypophysitis (HR 0.51; 95% CI 0.30-0.89; p = 0.018). The overall PFS at 12, 24 and 48 months was 36.75%, 25.69% and 22.72%, respectively. The results regarding PFS in relation to grade and number of toxicities are described in the table below. The correlation between OS and toxicity showed only a trend without statistical significance, due to the relative short follow-up and small number of pts. Conclusions: Our data show that patients who develop AEs and a greater number of different toxicities experience better PFS when treated with ICIs. The development of vitiligo, rash, pruritus and hypophysitis is associated with better PFS outcomes. We didn’t find a difference in PFS in pts who had grade 3-4 toxicity versus grade 1-2, unlike other series. Parameter HR 95% CI p-value Degree of toxicity  0 vs. Grade 1+2 0.39 0.28-0.54 <0.001  0 vs. Grade 3+4 0.37 0.24-0.58 <0.001  Grade 1+2 vs. 3+4 1.03 0.69-1.53 =0.87 Number of toxicities  0 vs. 1 0.47 0.32-0.68 <0.001  0 vs. 2 0.39 0.26-0.57 <0.001  0 vs. 3 0.34 0.20-0.56 <0.001  0 vs. ≥ 4 0.15 0.32-0.72 <0.001