Abstract
Sarcomatoid malignant pleural mesothelioma (MPM) is a rare and aggressive cancer with limited therapeutic options. We describe an exceptionally rare case of sarcomatoid MPM in a man in his 50s who developed three severe immune-related adverse events (irAEs)-Grade 3 pneumonitis, Grade 3 hepatitis, and Grade 4 agranulocytosis-within 55 days of initiating nivolumab plus ipilimumab. Corticosteroid treatment and granulocyte colony-stimulating factor resulted in recovery from these toxicities, while two liver biopsies provided essential diagnostic insights, distinguishing drug-induced liver injury from immune-related hepatitis. Despite receiving only a limited number of immune checkpoint inhibitor doses and discontinuing therapy, the patient exhibited rapid pleural tumor regression and sustained clinical benefit. This case highlights the potential association between severe immune-related side effects and favorable treatment response in MPM, and underscores the importance of pathology-supported diagnosis and shared decision-making in managing complex irAEs.