Document resource
Background and Importance Durvalumab and tremelimumab are monoclonal antibodies used as first-line systemic immunotherapy for advanced hepatocellular carcinoma (HCC). These agents are known to cause immune-mediated adverse drug reactions (ADRs), including severe pneumonitis, which can be life-threatening. Published reports on fatal autoimmune pneumonitis following this combination in HCC patients remain scarce. This case report describes a case of immune-mediated pneumonitis with fatal outcome.Aim and Objectives A 58-year-old male with obesity (history of sleeve gastrectomy), resolved diabetes and hypertension), NSAID allergy, and prior heavy smoking was diagnosed with a nodule of HCC in 11/2024 following investigations for abnormal liver function tests. After multidisciplinary evaluation, he underwent transarterial radioembolisation (TARE) as neoadjuvant treatment to surgery (01/2025). In the following month he experienced atrial fibrillation and a right-sided lacunar stroke, requiring apixaban. Further cardiac assessment in 05/2025 did not reveal significant coronary disease. HCC revaluation after TARE showed disease progression.Material and Methods In 06/2025, the patient began treatment with tremelimumab and durvalumab. Three weeks after the first cycle he developped cough and desaturation. When evaluated in the clinic for the second cycle of therapy, the patient was heavily symptomatic and was sent to ER. He underwent bronchoscopy and TC-scan revealing a bilateral interstitial pneumonitis. High-dose methylprednisolone and broad-spectrum antibiotics were initiated. Despite therapy, progressive respiratory failure required invasive ventilation in the ICU (07/2025). A clinical pharmacological evaluation was performed through a detailed medication review to identify potential drug interactions.Results Despite therapies and respiratory support, the patient’s condition deteriorated. Radiologic follow-up revealed increasing pulmonary consolidation, pericardial effusion, ascites, and futher worsening of HCC (TC-scan on 15/07/2025). Further escalation of vital support was excluded after multidisciplinary evaluation and the patient died on 18/07/2025. The Naranjo algorithm scored 6, indicating a probable causality for an immune-mediated ADR. No alternative causal factors emerged.Conclusion and Relevance This case details fatal immune-mediated pneumonitis as an adverse reaction to tremelimumab and durvalumab in HCC. The chronology, diagnostic exclusion, pharmacovigilance actions and medication review collectively reinforce the evidence for an immune-mediated mechanism. This case highlights the role of pharmacovigilance and systematic medication review in identifying and managing serious ADRs during cancer immunotherapy to enhance patient safety in these clinical settings.Conflict of Interest No conflict of interest