Abstract
Immune checkpoint inhibitors like pembrolizumab have transformed oncology but carry the risk of immune-related adverse events (irAE), including pneumonitis. We report a case of a 66-year-old male with multiple cardiac comorbidities who presented with acute hypoxic respiratory failure two months after discontinuing pembrolizumab due to repeated respiratory complaints. Imaging showed bilateral infiltrates and ground-glass opacities; infectious workup was negative. He was treated with corticosteroids for combined pembrolizumab-induced pneumonitis and diuretics for concurrent chronic heart failure exacerbation. Symptoms improved with supportive care and immunotherapy suspension. This case highlights the diagnostic challenge of differentiating irAE pneumonitis from infection or congestive heart failure (CHF) and underscores the need for early recognition in high-risk patients.