The Adverse Event of Interstitial Lung Disease in Patients Treated with Antibody-Drug Conjugates

Abstract Objectives There has been a yearly increase in the incidence of interstitial lung disease (ILD) adverse events associated with antibody-drug conjugates (ADCs), which is becoming a significant challenge for the clinical application of ADCs. We aim to conduct an exhaustive analysis of the clinical characteristics and outcomes of ADC-associated ILD in the real world. Methods We utilized the FDA Adverse Event Reporting System database spanning from January 2004 to September 2023 to evaluate the clinical characteristics, onset times, and outcomes of ADC-associated ILD adverse events in patients. Additionally, safety signals were generated using disproportionality and Bayesian analyses to evaluate the association between ADC and ILD. Results Out of the fifteen ADCs, ten were recorded to have caused ILD adverse events, accounting for a total of 643 reported cases. Eight ADCs exhibited statistically significant safety signals related to ILD in both disproportionality and Bayesian analyses. Trastuzumab deruxtecan recorded the highest reporting odds ratio (ROR) = 49.04 [95% confidence interval (CI) =44.41–54.17], proportional reporting ratio (PRR) = 43.90 (χ 2 = 18297.87), empirical Bayes geometric mean = 43.45 (95% one-sided CI, 39.98). 44.20% of adverse reactions were recognized within the first month of ADC treatment. The median time to onset for ILD related to gemtuzumab ozogamicin was notably the shortest at 4 days [interquartile range (IQR): 2–12 days], and it had the highest fatality proportion, standing at 57.14%. Conclusions This study analyzed demographic, temporal and outcome profiles of ADC-related ILD cases and identified high-risk signals. These findings help raise awareness and improve the monitoring of adverse events related to ADC. In the future, large-scale prospective studies are needed to further confirm and explore the underlying biological mechanisms.