Comparative real-world safety of nivolumab versus pembrolizumab in malignant melanoma: A propensity-matched cohort study.

Abstract

e21587 Background: Nivolumab and pembrolizumab are widely used programmed cell death-1 (PD-1) inhibitors approved for the treatment of malignant melanoma. Although both agents demonstrate comparable efficacy, real-world comparative safety data between these two therapies remain limited. We conducted a real-world cohort study to compare immune-related adverse events between nivolumab and pembrolizumab in patients with melanoma. Methods: We performed a retrospective cohort study using the TriNetX Global Collaborative Network, including adult patients (≥18 years) diagnosed with malignant melanoma treated with either nivolumab or pembrolizumab between January 2015 and December 2025. Patients receiving other immune checkpoint inhibitors were excluded. Propensity score matching (1:1) was used to balance baseline demographics and comorbidities, yielding 6,028 patients in each cohort. Outcomes assessed within three years after treatment initiation included pneumonia, inflammatory liver disease, autoimmune thyroiditis, type 1 diabetes mellitus, colitis, myocarditis, and dermatitis/eczema. Risk ratios, hazard ratios, Kaplan–Meier survival analyses, and number of event instances were evaluated. Results: After matching, baseline demographic and clinical characteristics were well balanced between the two cohorts. Nivolumab was associated with a significantly lower risk of pneumonia compared with pembrolizumab (risk ratio [RR] 0.89, 95% CI 0.81–0.99; hazard ratio [HR] 0.89, 95% CI 0.80–0.99). Rates of inflammatory liver disease, autoimmune thyroiditis, type 1 diabetes mellitus, colitis, and dermatitis were similar between groups, with no statistically significant differences observed. However, nivolumab was associated with a significantly higher risk of myocarditis compared with pembrolizumab (RR 2.31, 95% CI 1.29–4.15). Overall burden of immune-related adverse events was lower with nivolumab, with a reduced cumulative incidence of any immune-related adverse event (RR 0.93, 95% CI 0.87–0.99; HR 0.92, 95% CI 0.85–0.99). Conclusions: In this large real-world propensity-matched cohort of patients with malignant melanoma, nivolumab demonstrated a comparable overall safety profile to pembrolizumab, with lower risks of pneumonia and overall immune-related adverse events, but a higher risk of myocarditis. These findings provide clinically relevant real-world evidence to support individualized PD-1 inhibitor selection in melanoma.