Document resource
Background and Importance Ipilimumab/nivolumab is the first-line treatment for adults with advanced clear-cell renal carcinoma at intermediate/high risk. This case describes severe immune-mediated toxicity after one dose of ipilimumab (1 mg/kg) and nivolumab (3 mg/kg) in a stage IV patient who developed immune-mediated hepatitis and encephalitis. A complete review of the clinical record was conducted, and causality was assessed using the Naranjo algorithm.Aim and Objectives Ipilimumab/nivolumab can cause severe, potentially life-threatening immune-mediated adverse reactions. Early identification of the immune-mediated origin of hepatic and neurological alterations optimised corticosteroid therapy and improved patient safety.Material and Methods Ipilimumab/nivolumab can cause severe, potentially life-threatening immune-mediated adverse reactions. Early identification of the immune-mediated origin of hepatic and neurological alterations optimise corticosteroid therapy and improve patient safety.Toxicities were graded and managed following ASCO guidelines.Results 14/08/25: Fever hours after infusion, no infection source. Discharged with amoxicillin–clavulanate.20/08/25: New fever, mild C–reactive protein increase (8.9 mg/dL) and bilateral infiltrates on chest X–ray suggesting atypical pneumonia. Negative viral tests. Discharged with levofloxacin.24/08/25: Non–pruritic erythematous rash (grade 1). Treated with oral antihistamines.26/08/25: Readmitted for fever and worsening imaging. Chest CT showed bilateral ground–glass opacities suggesting grade 2 immune–mediated pneumonitis. Labs: AST 368, ALT 615, GGT 99; negative viral serologies. Diagnosis: grade 3 immune–mediated hepatitis. Prednisone 0.5 mg/kg initiated. Improvement and discharge (02/09/25).18/09/25: After cytoreductive nephrectomy, readmitted to intensive care for partial epileptic seizure (levetiracetam 1500 mg), immune–mediated encephalitis grade 3–4, acute hepatitis (AST 318, ALT 548, GGT 1025, bilirubin 3.45 mg/dL), and stage 2 acute kidney injury. Treated with methylprednisolone pulses (1 g/5 days) followed by prednisone 30 mg, achieving recovery.06/10/25: Mild transaminase increase, improved creatinine (1.32 mg/dL) and bilirubin (2.42 mg/dL). Asymptomatic. Plan: prednisone 30 mg/day for 2 weeks, then 15 mg/day.Causality scored 7 (probable).Conclusion and Relevance Severe immune-mediated hepatitis and encephalitis occurred after a single cycle. Discontinuation of immunotherapy and corticosteroid therapy led to full recovery. The early onset (≤12 days) and corticosteroid response confirmed a probable autoimmune mechanism. The next steps include strengthen pharmacovigilance for immune-mediated toxicities, train healthcare teams in early recognition, evaluate continuation of immunotherapy after ≥grade 3 events and share similar cases to expand knowledge on ipilimumab/nivolumab toxicities.Conflict of Interest No conflict of interest