A real-world pharmacovigilance analysis of cardiac adverse events associated with newer antibody-drug conjugates for hematological malignancies in adults: A disproportionality analysis from FDA adverse event reporting system database

IntroductionAntibody-drug conjugates (ADCs) are cancer therapies that deliver cytotoxic agents to tumor cells. Despite their specificity, toxicity remains a concern. Cardiac adverse events (CAEs) have not been studied in prospective trials, and guidance remains limited. We conducted a pharmacovigilance analysis using the FDA Adverse Event Reporting System (FAERS) to identify CAEs associated with ADCs for hematologic malignancies and assess high-risk subpopulations.MethodsWe analyzed five ADCs: gemtuzumab ozogamicin, inotuzumab ozogamicin, polatuzumab vedotin, loncastuximab tesirine, and belantamab mafodotin. CAEs were extracted from FAERS from each drug's approval through 2023. Disproportionality analysis used four metrics: reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC), and Empirical Bayes Geometric Mean (EBGM), with signals defined as significant across all.ResultsCAEs represented 3.2% of adverse events (AEs) for gemtuzumab, 2.0% for polatuzumab, 0.96% for inotuzumab, and 1.3% for belantamab. Polatuzumab showed signals for atrial tachycardia (ROR 30.96) and ventricular failure (ROR 10.42). Gemtuzumab showed signals for ventricular dysfunction (ROR 78.42) and myocardial ischemia (ROR 19.39). Inotuzumab indicated a significant signal in cardiotoxicity (ROR 5.43). Belantamab had no significant signals, and loncastuximab was excluded due to limited reports. Subgroup analysis showed increased CAEs among belantamab's approved indications (p < 0.01) and polatuzumab-associated hospitalizations (p = 0.01).ConclusionsOur study is the first to identify subpopulations disproportionately affected by ADC-associated CAEs. These results support the need for drug labeling and cardiac monitoring in high-risk groups. Prospective studies should inform evidence-based recommendations regarding ADC administration and cardiotoxicity risk.