Unusual Fatal Outcome Following Administration of a Combination of anti-PD1 and anti-CTLA4 in Metastatic Renal Cell Carcinoma: Liver Toxicity Case Report and a Literature Review.

Hepatic dysfunction, in the absence of liver metastases, occurs in 10-15% of renal cell carcinoma (RCC) patients, while immune hepatitis due to anti-CTLA4 and anti-PD1 administration affects about 3-9% and 0.7-1.8% of treated patients, respectively. Liver toxicity following combination therapy (anti-CTLA4 and anti-PD1) is seen in 29% of patients overall and grade 3-4 toxicity in 14% of patients. Stauffer's syndrome is a rare para-neoplastic phenomenon associated with RCC and characterized by abnormal liver function tests, hepato-splenomegaly and histological changes consistent with non-specific hepatitis. We describe a case of RCC treated with anti-CTLA4 and anti-PD1 therapy resulting in immediate liver toxicity and death after 2 months of progressive hepatic impairment. We hypothesize that high IL-6 levels due to Stauffer's syndrome might have contributed to immune-related hepatic failure. LEARNING POINTS: Consider Stauffer's syndrome in patients who develop liver toxicity unresponsive to immunotherapy.Evaluate IL-6 as high levels are seen in Stauffer's syndrome patients undergoing immunotherapy.Consider taking a liver biopsy to assess the severity of liver injury.