Progressive Fibrotic Pneumonitis Following Durvalumab Therapy: A Challenging Case

Durvalumab following chemoradiotherapy (CRT) is the standard of care for unresectable stage III non-small cell lung cancer (NSCLC). Immune-related pneumonitis (IrP) is a clinically relevant immune-related adverse event (irAE) that may limit treatment benefit and, although usually steroid-responsive, can rarely progress to chronic fibrotic lung disease. We report the case of a 71-year-old man with stage IIIc squamous NSCLC treated with CRT followed by consolidation durvalumab. After the second durvalumab cycle, he developed worsening dyspnoea, and computed tomography (CT) showed bilateral multifocal ground-glass opacities, consistent with IrP, without tumour progression. Durvalumab was discontinued, and high-dose corticosteroids were initiated. Despite initial partial improvement, the patient deteriorated during steroid taper, developing hypoxemic respiratory failure. A new CT demonstrated progressive interstitial involvement with evolution towards fibrotic changes. Escalation to intravenous methylprednisolone pulses led to improved gas exchange, although dyspnoea persisted. Nintedanib was introduced as an antifibrotic therapy, achieving radiographic stabilisation. Nonetheless, clinical improvement remained limited, and four months later, restaging imaging demonstrated oncological progression, and palliative care was adopted. This case illustrates the diagnostic and therapeutic challenges of IrP after CRT and durvalumab, particularly when fibrosis predominates, and steroid-refractory progression occurs. Early recognition, close surveillance and timely multidisciplinary management should be warranted, and antifibrotic therapy may be considered in cases of fibrotic evolution despite immunosuppressive treatment.