Adverse events of antibody-drug conjugates: comparative analysis of agents with a common payload using the adverse event spontaneous reporting database.

BACKGROUND

Antibody-drug conjugates (ADCs) have been implicated in myelosuppression and peripheral neuropathy (PN), possibly owing to their payload. Thus, their systemic toxicity should be considered. However, reports documenting adverse event (AE) occurrences in clinical settings are limited. This study analyzed AEs associated with polatuzumab vedotin, brentuximab vedotin, and enfortumab vedotin-which share a common payload-based on patient background factors using Japanese and United States AE spontaneous reporting databases.

MATERIALS AND

METHODS

This study examined data from the Japanese Adverse Drug Event Report database (April 2004-June 2023) and the Food and Drug Administration AE Reporting System (first quarter of 1997-third quarter of 2023). Safety signals for an AEs were defined as a reporting odds ratio lower limit of the 95% confidence interval >1. Additionally, AEs were stratified based on sex, age, and body mass index to explore correlations between patient demographics and AEs.

RESULTS

Signals of PN, myelosuppression, and febrile neutropenia were detected in all ADCs. Polatuzumab vedotin showed earlier PN onset than other drugs and rare AEs such as heart failure. Enfortumab vedotin had widely detected skin-related AEs. Stratified analysis showed more AEs in males aged ≥60 years.

CONCLUSIONS

Our study identifies common AEs, including PN and myelosuppression in ADCs sharing the same payload. Onset duration and outcomes of each AE vary among ADCs.