Respiratory Disorders Associated with Antibody–Drug Conjugates: A Combined Analysis of the French and the WHO Pharmacovigilance Databases

Antibody–drug conjugates are proving to be highly effective in oncology, yet their real‐world respiratory safety profile remains largely unknown. This study sought to characterize drug‐linked respiratory disorders and identify safety signals. We performed a descriptive analysis with expert review of respiratory adverse drug reactions related to antibody–drug conjugates from the French pharmacovigilance database. We also conducted disproportionality analyses for interstitial lung disease, pulmonary arterial hypertension, and pleural disorder using VigiBase®. Among the 71 patients included in the descriptive study, 56 (78.9%) were women, and the median age was 60 years. Most (71.8%) were treated for breast cancer. Fifty‐nine patients (83.1%) developed antibody–drug conjugate‐related interstitial lung disease, primarily after trastuzumab deruxtecan. Nine patients (12.7%) developed pulmonary arterial hypertension and three (4.2%) contracted pleural disorders, mainly after trastuzumab emtansine. The median time to onset varied by clinical feature, with 1 month for pleural disorder, 4 months for interstitial lung disease, and 45 months for pulmonary arterial hypertension. The disproportionality analysis showed a significant signal for interstitial lung disease with brentuximab vedotin, polatuzumab vedotin, trastuzumab emtansine, and trastuzumab deruxtecan. Only trastuzumab emtansine had a significant signal for pulmonary arterial hypertension. All antibody–drug conjugates, except belantamab mafodotin and enfortumab vedotin, were associated with a significant signal for pleural disorders. Our study highlights the risk of interstitial lung disease with these drugs in real‐world settings and identified pulmonary arterial hypertension and pleural disorders as additional safety signals. Further research is needed to confirm these findings in population‐based studies and to identify antibody–drug conjugates and patient‐related risk factors.