Cardiovascular and oncologic outcomes of nivolumab + ipilimumab vs. pembrolizumab in malignant melanoma: A global real-world data analysis.

Abstract

e21538 Background: Malignant melanoma is a highly aggressive cancer often treated with immune checkpoint inhibitors. While nivolumab + ipilimumab and pembrolizumab are established therapies, their cardiovascular safety profiles remain a concern. This study leverages global real-world data to compare the cardiovascular risks associated with these regimens and aid in providing individualized treatment for patients. Methods: Using a real-world global database, we identified malignant melanoma patients (2005–2024) and stratified them into two cohorts: nivolumab + ipilimumab combination therapy or pembrolizumab monotherapy. Propensity score matching was applied to balance demographics and comorbidities. Primary and secondary cardiovascular, endocrine, and renal outcomes were assessed using the platform analytical tools. Risk Ratios (RR) with 95% confidence interval (CIs) and p-values were calculated. Results: A total of 26,669 patients were analyzed, with 11,441 patients in each matched cohort. Hypertension and diabetes were the most common comorbidities. Combination therapy was associated with a slightly higher mortality risk than pembrolizumab monotherapy (RR: 1.08, 95% CI: 1.04–1.12, p < 0.001). The incidence of acute MI (RR: 1.01, p = 0.81) and cardiac arrest (RR: 0.95, p = 0.74) did not differ significantly between groups. Combination therapy was linked to a lower risk of new heart failure (RR: 0.88, p = 0.001) and atrial fibrillation/flutter (RR: 0.87, p < 0.001). The risk of acute hemorrhagic stroke was significantly higher in the combination therapy group (RR: 2.89, p < 0.001), while ischemic stroke risk was not significantly different (RR: 1.2, p = 0.22). Secondary malignancies were more frequent in the combination therapy cohort (RR: 1.15, p < 0.001). Rates of HLH (RR: 1.5, p = 0.32), hypothyroidism (RR: 1.07, p = 0.001), and AKI (RR: 1.1, p < 0.001) varied between groups, while readmission rates were comparable (RR: 0.9, p = 0.52). Conclusions: Real-world data shows similar cardiovascular outcomes between nivolumab + ipilimumab and pembrolizumab, with slightly higher mortality in the combination therapy group likely due to increased risk of hemorrhagic stroke and secondary malignancies in the real-world setting. Pembrolizumab monotherapy is also a reasonable option, highlighting the need for individualized treatment based on patient characteristics.