Assessing safety concerns of interstitial lung disease associated with antibody-drug conjugates: a real-world pharmacovigilance evaluation of the FDA adverse event reporting system

Background: Antibody-drug conjugates have revolutionized cancer therapy due to their selectivity and efficacy. However, concerns have been raised regarding the potential effects of trastuzumab deruxtecan in interstitial lung diseases.

Aim: This study aimed to investigate the safety signals and time to onset of antibody-drug conjugates induced interstitial lung disease.

Method: We utilized the FDA Adverse Event Reporting System database (2004-2022) to identify interstitial lung disease safety signals in 13 FDA-approved antibody-drug conjugates. Disproportionality analysis was conducted to estimate the reporting odds ratios for interstitial lung disease.

Results: Seven antibody-drug conjugates exhibited safety signals of interstitial lung disease: trastuzumab deruxtecan [reporting odds ratio, ROR (95% confidence intervals, CI) = 64.15 (57.07-72.10)], enfortumab vedotin [ROR (95% CI) = 5.24 (3.25-8.43)], trastuzumab emtansine [ROR (95% CI) = 3.62 (2.90-4.53)], brentuximab vedotin [ROR (95% CI) = 3.22 (2.49-4.17)], polatuzumab vedotin [ROR (95% CI) = 2.56 (1.59-4.12)], gemtuzumab ozogamicin [ROR (95% CI) = 2.53 (1.70-3.78)], and inotuzumab ozogamicin [ROR (95% CI) = 2.33 (1.21-4.49)]. Five antibody-drug conjugates with limited reports were excluded from further analysis: belantamab mafodotin, loncastuximab tesirine, mirvetuximab sorafenib, tisotumab vedotin, and moxetumomab pasudotox. Japan and the United States were the primary reporting countries.

Conclusion: This real-world study highlights high safety signals of interstitial lung disease associated with antibody-drug conjugates. Clinicians should be aware of these safety concerns and risk factors and implement early identification measures for their patients. Future research should prioritize comprehensively exploring the relationship between antibody-drug conjugates and lung diseases.