Heterogeneity of Response and Immune System Activity during Treatment with Nivolumab in Hepatocellular Carcinoma: Results from a Single-Institution Retrospective Analysis

SIMPLE SUMMARY: Immunotherapy is an emerging treatment in hepatocellular carcinoma, both alone and in combination. The advent of this new approach raises challenges for the interpretation of response assessment due to the peculiar patterns of mixed responses, pseudoprogression and hyperprogression. Furthermore, there are no criteria to drive selection of treatment strategy. We analyzed data from the first 10 patients treated with nivolumab in our institution and we identified different patterns of response according to the lesion’s site. Furthermore, we analyzed blood samples from the first four patients, and found differences, between a patient with shorter survival and the other three, that may provide insight into mechanisms underlying the different activities of nivolumab. Although we analyzed data from a small number of patients, our results can help to understand mechanisms of immunotherapy activity in order to define the most appropriate treatment strategy for each patient. ABSTRACT: Treatment of hepatocellular carcinoma (HCC) is rapidly evolving, with many new therapeutic options; in particular, immunotherapy (IT) is acquiring a major role, even in combination regimens. Despite these promising results, an important limitation is the lack of prognostic and predictive factors that prevent provision of a tool for patient stratification in order to select the most appropriate strategy. Furthermore, response assessment can be challenging with IT due to peculiar patterns such as mixed responses or pseudoprogression. We analyzed biological and clinical features from the first 10 HCC patients treated with nivolumab in our institution. Analysis of patterns of response in CT assessment revealed complete response in pulmonary lesions, along with heterogeneous behavior in the liver and other organ lesions. Peripheral blood mononuclear cells (PBMC) analysis in the first four patients showed unique alterations in a patient with poor prognosis, both at baseline (lower percentage of effector T cells, higher percentage of natural killer T [NK/T] cells) and during treatment with nivolumab (decrease in nonclassical monocytes, increase in monocytic myeloid-derived suppressor cells [MO-MDSC]), suggesting a possible prognostic role for these features. Although obtained in a small cohort of patients, our results open a new perspective for understanding mechanisms underlying IT outcomes in HCC patients.