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

Lilong Zhang; Jiarui Feng; Tianrui Kuang; Dongqi Chai; Zhendong Qiu; Wenhong Deng; Keshuai Dong; Kailiang Zhao; Weixing Wang

doi:10.1016/j.intimp.2023.110019

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

Int Immunopharmacol. 2023 May:118:110019. doi: 10.1016/j.intimp.2023.110019. Epub 2023 Mar 16.

Authors

Lilong Zhang¹, Jiarui Feng¹, Tianrui Kuang¹, Dongqi Chai¹, Zhendong Qiu¹, Wenhong Deng¹, Keshuai Dong¹, Kailiang Zhao², Weixing Wang³

Affiliations

¹ Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, China; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, China; Hubei Key Laboratory of Digestive System Disease, Wuhan, China.
² Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, China; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, China; Hubei Key Laboratory of Digestive System Disease, Wuhan, China. Electronic address: zhaokl1983@whu.edu.cn.
³ Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, China; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, China; Hubei Key Laboratory of Digestive System Disease, Wuhan, China. Electronic address: wangwx@whu.edu.cn.

PMID: 36933492
DOI: 10.1016/j.intimp.2023.110019

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.

Keywords: Blood biomarkers; Hepatocellular carcinoma; Immune checkpoint inhibitors; Outcomes.

Publication types

Meta-Analysis

MeSH terms

Biomarkers
Carcinoma, Hepatocellular* / drug therapy
Humans
Immune Checkpoint Inhibitors / therapeutic use
Liver Neoplasms* / drug therapy
Prognosis
Retrospective Studies
alpha-Fetoproteins

Substances

alpha-Fetoproteins
Immune Checkpoint Inhibitors
Biomarkers