Respiratory Disorders Associated with Antibody–Drug Conjugates: A Combined Analysis of the French and the <scp>WHO</scp> 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.