Abstract 18533: Exploring the Rising Incidence of Myocarditis and Other Cardiovascular Adverse Events of Nivolumab and Ipilimumab: Analysis of FDA Adverse Event Reporting System Database

Abstract

Introduction: Nivolumab and Ipilimumab are human monoclonal antibodies that target cell surface PD1 and anti-CTLA-4 receptors respectively. Nivolumab and ipilimumab combination is used for metastatic small cell lung carcinoma, advanced renal cell carcinoma and metastatic melanoma. The pre-approval CHECKMATE trials have underestimated the occurrence of cardiovascular adverse events (AEs). In contradiction, post-marketing studies have demonstrated a higher incidence of cardiac AEs, particularly myocarditis.Therefore, it is important to establish a post-marketing safety profile of these medications. Methods: We investigated the cardiovascular AEs of nivolumab and ipilimumab using U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). Healthcare professionals (HCPs) reported 79.73% and 80.92% of AEs until March 2023 for nivolumab and ipilimumab respectively. We conducted further subgroup analysis of cardiovascular AEs in male, females as well as in three age groups: 18-64, 65-85 and >85 years. Results: Amongst the cardiovascular AEs reported by HCPs, myocarditis was reported in 905 (1.55 %) in nivolumab vs 445 (1.72%) in ipilimumab group. There were higher reports of other cardiovascular AEs including heart failure (1.15% vs 0.74%), pericarditis/pericardial effusion (1.19% vs 0.6% ), myocardial infarction (0.18% vs 0.71%), cardiomyopathy (0.36% vs 0.29%), cardiac arrest (0.41% vs 0.53%) and cardiac death (0.01% vs 0.02%) in nivolumab vs ipilimumab. On sub-group analysis, we observed higher incidence of myocarditis in females (1.54% vs 1.6%) males (1.73% vs. 1.84%) and in patient with age 18-65 years (1.17% vs 1.15%) in both nivolumab vs ipilimumab group as compared to previous studies. Conclusions: The reported events of myocarditis were significantly higher in FAERS reporting as compared to the CHECKMATE trials (<1%) in both nivolumab and ipilimumab groups. Clinicians need to be vigilant in detecting immune-mediated myocarditis, as it often manifests with nonspecific symptoms, with early onset and rapid progression. Given the growing utilization of these medications, it is imperative to conduct additional randomized controlled trials to gain a better understanding of their cardiovascular safety profile.