Characterization of tumor mutation burden, PD-L1 and hepatitis B virus in Chinese hepatocellular carcinoma patients.

Abstract

e15666 Background: Hepatocellular carcinoma (HCC) has a high mortality rate and is the fourth most common cancer in China. Immunotherapy of immune checkpoint inhibitors (ICI) is a promising novel treatment strategy, but the response rate is generally low and it is not clear which patients will benefit from ICI immunotherapy. Methods: Deep sequencing targeting 450 cancer genes was done on FFPE and matched blood samples from 601 Chinese HCC patients (pts). Genomic alterations including single nucleotide variations, short and long insertions/deletions, copy number variations (CNV), gene rearrangements and fusions were analyzed. Tumor mutation burden (TMB) was measured by an algorithm developed in-house, PD-L1 expression was done by immunohistochemistry staining and Hepatitis B Virus (HBV) by target capture. Results: Patients, median age 55 years old, had TMB values in a range of 0.7 to 69.6 Muts/Mb. The 1st Quartile, median and 3rd Quartile TMB values were 3.8, 5.4 and 7.8 Muts/Mb, respectively. Comparing 155 pts with TMB-H (≥3rd Quartile) to 181 TMB-L (≤1st Quartile) pts, the mutant frequencies of TERT (49% vs 38%, p= 0.044), CTNNB1 (32% vs 11%, p< 0.001), LRP1B (14% vs 5%, p= 0.004) and ARID1A (12% vs 5%, p= 0.014) were higher. The mutant frequency of TP53 was lower (57% vs 68%, p= 0.035). TMB-L had younger pts (median age 50y vs 60y, p< 0.001) and CNV (382 vs 232, p< 0.001). PD-L1 expression was detected seen in 222 pts, including 152 pts of Dako 28-8 Ab and 70 pts of Dako 22C3 Ab with no preference. The PD-L1 positive rate (TPS ≥1%) was 7% and 34% in 28-8 group and 22-C3 group, respectively. Eleven pts were both TMB-H and PD-L1 positive. HBV probe signal was detected in 285 pts, 262 of which were positive (≥10 reads). TMB, PD-L1 expression and HBV were not found to be significantly correlated. Conclusions: In our study, 37% of Chinese HCC pts with PD-L1 positive or TMB-H may benefit from immunotherapy. TMB-H HCC pts were older, had more common TERT, CTNNB1, LRP1B and ARID1A mutations, and fewer TP53 mutations and CNV. In our current cohort, TMB and PD-L1, TMB and HBV, and PD-L1 expression and HBV were not correlated significantly.