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

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.