299: Immune Checkpoint Inhibitor-Related Multiorgan Toxicity

Introduction: Immune checkpoint inhibitors (ICIs) like durvalumab have transformed treatment for non-small cell lung cancer (NSCLC). However, they can cause serious immune-related adverse events (irAEs), including pneumonitis and colitis. While each may occur alone, multi-organ involvement is rare. We report a severe case of ICI-induced pneumonitis followed by fulminant colitis with colonic perforation requiring surgery. Description: A 74-year-old man with chronic obstructive pulmonary disease (on 2L oxygen) and stage IIIA PD-L1 90% squamous cell carcinoma of the left lung, diagnosed in November 2023, completed chemoradiation in April 2024 and started durvalumab in June 2024. He was hospitalized in August 2024 with fever, chills, weakness, and worsening dyspnea. He was hypoxic and hypotensive, requiring high-flow oxygen. Imaging showed pneumonitis; infection workup was negative but inflammatory markers were elevated. He was treated for immune checkpoint inhibitor (ICI)-related pneumonitis with IV methylprednisolone (125 mg q6h, then 60 mg q6h), with subsequent clinical improvement. On hospital day 6, just before discharge, he developed abdominal pain and diarrhea. CT revealed acute colitis involving the cecum and ascending colon. Due to peritoneal signs, he underwent exploratory laparotomy, which showed patchy necrosis. A right hemicolectomy with primary anastomosis was performed. Histopathology confirmed ICI-related colitis with transmural inflammation and lymphocytic infiltration. Steroid taper was continued post-op. Durvalumab was discontinued. Five months later, the patient’s cancer progressed to stage IV with brain and pleural metastases, and he was transitioned to palliative radiotherapy and chemotherapy. Discussion: This case illustrates severe, multisystem immune-related adverse events (irAEs) associated with ICIs. Pneumonitis, affecting 3–5% of durvalumab patients, typically presents with nonspecific respiratory symptoms. Colitis is less common (1–2%), and progression to necrosis and perforation is rare. Prompt imaging and surgical intervention are critical in such cases. These complications can arise at any time within several months of initiating ICI therapy, underscoring the need for ongoing vigilance.