Adverse Events in Patients with Melanoma Treated with Immune Checkpoint Inhibitors: A Real-World Ambispective Cohort Analysis

Background: Immune checkpoint inhibitors (ICIs) are effective against melanoma, but are often limited by adverse events (AEs). We aimed to characterise the incidence, characteristics and predictors of AEs. Methods: This ambispective study included 141 patients with melanoma (165 ICI treatment episodes) treated between March 2017 and April 2026. Predictors of AE occurrence, seriousness and severity were analysed per treatment episode and per AE using generalised estimating equations. Results: We recorded 206 AEs in 95 patients (67.4%). At least one AE occurred in 59.8% of pembrolizumab, 59.5% of nivolumab and 81.0% of nivolumab/ipilimumab episodes. Most AEs were Grade 1–2 (88.3%); skin disorders were the most frequent (29.1%) and endocrine AEs had the lowest resolution rate (3.2%). Time to first AE was shortest with nivolumab/ipilimumab (p < 0.001). Per episode, nivolumab/ipilimumab was associated with more serious AEs than nivolumab (p = 0.042) and, borderline, than pembrolizumab (p = 0.051), and with Grade 3–4 AEs (p = 0.001); the lower odds of AE with monotherapy were not significant (p = 0.063, 0.242). Systemic treatment for unresectable disease was associated with AE occurrence (p = 0.029), serious (p = 0.009) and Grade 3–4 AEs (p = 0.016), and BRAF mutation with AE occurrence (p = 0.029). Conclusions: Patients receiving combination immunotherapy and those treated for unresectable disease may warrant closer monitoring.