Key result
Hematologic antibody-drug conjugates linked to cardiac events, notably ~78-fold higher ventricular dysfunction with gemtuzumab.
Why the study?
Cardiac adverse events associated with antibody-drug conjugates for hematologic malignancies have not been evaluated in prospective trials, leaving clinical guidance limited.
Are newer antibody-drug conjugates for hematological malignancies associated with disproportionate reporting of cardiac adverse events?
Observational
Are newer antibody-drug conjugates for hematological malignancies associated with disproportionate reporting of cardiac adverse events?
Pharmacovigilance analysis reveals significant signals for cardiac adverse events, including ventricular dysfunction and atrial tachycardia, associated with specific antibody-drug conjugates used for hematological malignancies, highlighting the need for cardiac monitoring.
Alerts clinicians to potential CAE risks with ADCs; leaves open need for prospective validation in hematologic malignancies.
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.
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Dilip et al. (2026) conducted an observational in Hematological malignancies. Antibody-drug conjugates vs. Other drugs in the FAERS database was evaluated on Cardiac adverse events (CAEs). Antibody-drug conjugates for hematological malignancies showed significant cardiac adverse event signals, including ventricular dysfunction with gemtuzumab (ROR 78.42).
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