Bispecific T-cell engagers-induced interstitial lung disease: two case reports confirmed by transbronchial lung cryobiopsy

Introduction: Drug-induced interstitial lung disease (DI-ILD) is a severe pulmonary condition associated with various drugs. Bispecific T-cell engagers (BiTEs) are a new class of immunotherapy used in the treatment of hematologic malignancies. We describe 2 cases of interstitial lung disease related to BiTE therapy (epcoritamab and glofitamab) in 2 patients with non-Hodgkin lymphomas. Case Presentation: Both patients presented with subacute respiratory symptoms and ground-glass opacities on chest CT. Bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial lung cryobiopsy (TBLC) was performed. BAL revealed a predominant CD8+ lymphocytosis with a reduced CD4/CD8 ratio. Histological examination showed features consistent with a nonspecific interstitial pneumonia (NSIP)-like pattern. Other causes of ILD including infections and autoimmune disorders were excluded, and a diagnosis of BiTE-induced interstitial pneumonia was eventually made. Initiation of systemic corticosteroids led to clinical and radiological improvement in both cases. Conclusion: These findings suggest that BiTEs may trigger immune-mediated pulmonary toxicity, and highlight the diagnostic value of TBLC in suspected cases of drug-related ILD.