Blood biomarkers predict outcomes in patients with hepatocellular carcinoma treated with immune checkpoint Inhibitors: A pooled analysis of 44 retrospective sudies.

ABSTRACT

OBJECTIVE: We conducted the first meta-analysis to identify the predictive significance of baseline blood biomarkers (such as neutrophil to lymphocyte ratio (NLR), early alpha-fetoprotein (AFP) response, albumin-bilirubin (ALBI), AFP, platelet to lymphocyte ratio (PLR), C-reactive protein (CRP), protein induced by vitamin K absence II (PIVKA-II), and lymphocyte to monocyte ratio (LMR)) in hepatocellular carcinoma (HCC) patients treated with immune checkpoint inhibitors (ICIs). METHODS: Eligible articles were retrieved using PubMed, the Cochrane Library, EMBASE, and Google Scholar by November 24, 2022. Clinical outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and hyperprogressive disease (HPD). RESULTS: A total of 44 articles with 5322 patients were included in this meta-analysis. The pooled results demonstrated that patients with high NLR levels had significantly poorer OS (HR 1.951, P < 0.001) and PFS (HR 1.632, P < 0.001), lower ORR (OR 0.484, P < 0.001) and DCR (OR 0.494, P = 0.027), and higher HPD (OR 8.190, P < 0.001). The patients with high AFP levels had shorter OS (HR 1.689, P < 0.001) and PFS (HR 1.380, P < 0.001), and lower DCR (OR 0.440, P < 0.001) than those with low AFP levels, however, there was no difference in ORR (OR 0.963, P = 0.933). We also found that early AFP response was correlated with better OS (HR 0.422, P < 0.001) and PFS (HR 0.385, P < 0.001), higher ORR (OR 7.297, P < 0.001) and DCR (OR 13.360, P < 0.001) compared to non-responders. Besides, a high ALBI grade was significantly related to shorter OS (HR 2.440, P = 0.009) and PFS (HR 1.373, P = 0.022), lower ORR (OR 0.618, P = 0.032) and DCR (OR 0.672, P = 0.049) than those with an ALBI grade 1. CONCLUSION: The NLR, early AFP response, and ALBI were useful predictors of outcomes in HCC patients treated with ICIs.