Abstract
BACKGROUND: Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1) and cytotoxic T lymphocyte associated protein 4 (CTLA-4) have significantly improved the treatment of non-small cell lung cancer (NSCLC), offering new therapeutic options. However, immune-related adverse events (irAEs), particularly immune checkpoint inhibitor-related pneumonitis (ICI-P), remain a serious concern. Bispecific antibodies targeting both programmed death-ligand 1 (PD-L1) and CTLA-4 have recently emerged as promising alternatives to traditional dual ICI therapies, offering comparable efficacy with a potentially lower risk of irAEs. We report the first documented case of ICI-P induced by a bispecific antibody targeting PD-L1 and CTLA-4 in a patient with NSCLC, with a comprehensive account of the diagnostic process and therapeutic management. CASE DESCRIPTION: A 64-year-old man with stage IV lung squamous cell carcinoma was enrolled in a clinical trial of KN046 combined with chemotherapy. After three treatment cycles, he developed symptoms of ICI-P, including cough and dyspnea, which were confirmed by chest computed tomography (CT) and laboratory testing. His symptoms worsened despite initial corticosteroid therapy. Tocilizumab and nintedanib were subsequently added, resulting in rapid clinical and radiologic improvement. This case highlights the potential role of nintedanib in managing corticosteroid-refractory ICI-P, a challenging complication of ICI therapy. CONCLUSIONS: This case represents the first reported instance of ICI-P induced by a bispecific antibody targeting PD-L1 and CTLA-4, with a comprehensive account of its clinical course and management. Compared to conventional dual ICI regimens, bispecific antibodies may offer a more favorable safety profile. The observed benefit of nintedanib in this corticosteroid-refractory case suggests a potential role for anti-fibrotic therapy in managing early fibrotic changes. Further clinical studies are needed to validate this approach.