Abstract

Background: Immune checkpoint inhibitors (ICIs), including anti-PD1 & anti-CTLA4, are pivotal in treating melanoma, utilized both in advanced and adjuvant therapies. These ICIs can induce a range of immune-related adverse events (irAEs) affecting various organs, primarily the skin, gastrointestinal tract, endocrine glands, liver, lung, & musculoskeletal system. While generally manageable, irAEs can sometimes lead to treatment discontinuation or, rarely, be fatal. Combined anti-CTLA4/anti-PD1 therapy shows higher irAE frequencies & severity compared to monotherapies. steroids are standard for managing most irAEs, with other immunomodulators effective in steroid-refractory cases. The study also examines the prognostic role of irAEs in melanoma & the impact of steroids & immunomodulators on clinical outcomes. Methods: A retrospective single-centre cohort study, including 149 melanoma patients treated with ICIs. The study analyzed the onset, grade, and resolution of irAEs, along with their treatment approaches. Time-to-event outcomes (duration of corticosteroids and immunosuppressive agents, time to resolution, Overall Survival (OS), progression-free survival (PFS) were visualized by Kaplan–Meier curve Results: Demographics: 149 patients were analyzed, with 73.6% in palliative and 26.3% in an adjuvant setting. The median age was 64 years. Adverse Events: A high incidence of irAEs was observed across different treatment regimens. The most common were thyroiditis, colitis, and rash. Severe toxicities were more common in combined immunotherapy. Treatment-related Toxicities: In the non-adjuvant/unresectable setting, 64.6% of patients experienced toxicities, leading to discontinuation in 21% of cases. In the adjuvant setting, 66.7% experienced adverse events, with 22% discontinuing treatment. Efficacy: In the non-adjuvant setting, patients with irAEs showed more favourable progression-free survival (PFS) across all treatment regimens (p = 0.0036 for anti-CTLA4, p = 0.0022 for anti-PD1, p < 0.0001 for combined therapy).OS also showed benefits except for anti-PD1 (p = 0.22). Immunomodulatory Agents: Treatment with steroids and immunomodulatory agents did not significantly impact PFS or OS in both settings. Conclusions: The presence of irAEs is correlated with increased treatment efficacy in the palliative setting for melanoma. The use of steroids and immunomodulatory agents does not affect ICI efficacy. This suggests that irAEs could be considered as potential prognostic markers for ICI treatment in melanoma.