Cardiotoxicity of antibody–drug conjugates: A FAERS-based pharmacovigilance study (2023–2024).

443 Background: Antibody–drug conjugates (ADCs) are an emerging class of cancer therapies that enable targeted delivery of cytotoxic agents to tumor cells. However, cardiovascular adverse events (AEs) have become increasingly recognized with ADC use. Despite growing concern, the incidence and characteristics of ADC-associated cardiotoxicity remain insufficiently studied. This analysis aimed to characterize the cardiotoxicity profile of ADCs using data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: We conducted a retrospective pharmacovigilance study using FAERS data from 2023–2024. Cardiotoxic events were defined using MedDRA Preferred Terms, including cardiac failure, myocarditis, pericardial effusion, arrhythmia, cardiomyopathy, left ventricular dysfunction, QT prolongation, and heart rate irregularity. Reports mentioning any ADCs were identified. Descriptive statistics were generated, and disproportionality analysis was performed using Reporting Odds Ratios (RORs) compared to the full FAERS dataset, with statistical analyses conducted in R (v4.5.0). Results: Of 3,727 FAERS reports involving ADCs, 31 (0.83%) included cardiotoxic events, compared to 3,696 (0.23%) among 1,620,445 non-ADC reports. The overall mortality rate in ADC-associated reports was 22.78% (848 deaths). Disproportionality analysis showed no statistically significant association between ADC use and cardiotoxicity (Risk Ratio = 0.9999; 95% CI: 0.9991–1.0006; p = 0.860). The most frequently reported cardiotoxic events with ADCs were cardiac failure (n=10), arrhythmia (n=7), cardiomyopathy (n=5), and myocarditis (n=3). Less common events included pericardial effusion, QT prolongation, left ventricular dysfunction, and heart rate irregularity. Conclusions: Although cardiotoxic events with ADCs were rare, the elevated mortality rate among affected patients is concerning. While disproportionality analysis did not identify a significant safety signal, these findings highlight the need for continued pharmacovigilance and cardiac monitoring in patients receiving ADC therapy.