An exceptional response to immunotherapy doublet in combined hepatocellular carcinoma-cholangiocarcinoma

Abstract

Abstract Background We present here a case of a 67-year-old male. He presented in May 2018 with severe abdominal pain and weight loss of 25%. Alpha-feto protein (AFP) and Carbohydrate antigen 19-9 (CA19-9) were within normal limits, and CA125 was 5 times upper normal limit (ULN). Computed tomography showed liver masses and enlarged retroperitoneal lymph nodes. Biopsy from a liver mass showed Combined Hepatocellular Carcinoma (HCC)-Cholangiocarcinoma (CC) (CHC). This a rare tumor, with an incidence of less than 10% of primary liver tumors. In whole exome analysis, mutations suggested the bipotent cell origin and stem cell origin. There are no guidelines or randomized trials regarding treatment. In an analysis of 36 patients who were treated with chemotherapy, the progression-free survival was 2.8 months, with an overall response rate of 5.6%. Targeted agents had minimal effect on survival. Methods In our case, extensive genomic, transcriptomic and proteomic testing was performed. No genomic alterations were identified, tumor mutational burden was low and microsatellite status was stable. 7 of 9 immune checkpoint genes were overexpressed. A variant in CDK12 was noted, which was shown to be associated with elevated neoantigen burden and may predict benefit from immune checkpoint therapy. Results The patient began immunotherapy with ipilimumab and nivolumab followed by nivolumab, which he is continuing. The only side effects were hypothyroidism and Addison’s disease which are being treated. His clinical response was dramatic, he regained all the lost weight, and discontinued high dose opiate treatment. ECOG performance status improved from 3 to 0. Repeated PET-CT showed near complete response, ca125 decreased by 90% and liver function tests normalized. Table: 49P . Blood tests of case Before immunotherapy After 11 months of immunotherapy Normal range Alk Phos 456 83 38-150 GGT 588 72 15-73 Ca125 210 21 2-35 Conclusions We present here an exceptional case of a rare tumor, where the patient had a clinical, laboratory and radiological response and a significant improvement in quality of life, suggesting that these tumors are sensitive to immunotherapy. No published cases of this tumor have yet been treated with immunotherapy doublet. Legal entity responsible for the study The author. Funding Has not received any funding. Disclosure The author has declared no conflicts of interest.