Enfortumab vedotin induced interstitial lung disease: A first case report with pathological evidence from transbronchial lung cryobiopsy

Enfortumab vedotin (EV), an antibody–drug conjugate targeting Nectin-4, has demonstrated efficacy against advanced urothelial carcinoma. While initially considered rare, EV-induced interstitial lung disease (ILD) is increasingly recognized, yet its pathological features remain poorly characterized. We report a case of a 60-year-old man with metastatic urothelial carcinoma who developed fever, fatigue, and cough after two cycles of EV therapy. His treatment history included right nephroureterectomy, platinum-based chemotherapy, and immune checkpoint inhibitors nivolumab and pembrolizumab. Laboratory tests revealed elevated serum ILD markers (Krebs von den Lungen-6527.7 U/mL, surfactant protein-D 294.5 ng/mL), and chest computed tomography showed new infiltrative shadows with air bronchogram predominantly in subpleural regions of the right lower lobe, consistent with organizing pneumonia pattern. Bronchoalveolar lavage from the right middle lobe showed 92 % macrophages with negative cultures. Transbronchial lung cryobiopsy revealed fibrosing nonspecific interstitial pneumonia with prominent fibrosis around bronchovascular bundles, lymphocytic infiltration in vessel walls and alveolar septa with myxofibrous thickening, epithelial injury, and fibrin exudation into alveolar spaces—representing previously undocumented features of EV-induced ILD. Drug discontinuation alone proved insufficient, but the patient improved markedly with methylprednisolone pulse therapy. This case highlights two key findings: detailed histopathological characterization through cryobiopsy documents distinct pathological features of EV-induced ILD; and early bronchoscopic evaluation helped guide therapeutic decision-making, supporting aggressive corticosteroid therapy. These findings advance our understanding of both the pathological features and management of EV-induced ILD, particularly relevant as EV–pembrolizumab combination becomes standard first-line treatment.