Journal of Hepatocellular Carcinoma (Nov 2023)
Early C‐reactive Protein Kinetics Predict Response to Immune Checkpoint Blockade in Unresectable Hepatocellular Carcinoma
Abstract
Qiuying Qin,1,2,* Xiaoxuan Kou,1,2,* Yuanyuan Zheng,1,2 Fei Zhou,1,2 Xiaoyong Zhang,1,2 Hongyan Liu1,2 1State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 2Key Laboratory of Infectious Diseases Research in South China (Southern Medical University), Ministry of Education, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoyong Zhang; Hongyan Liu, Email [email protected]; [email protected]: In recent years, a new therapeutic approach, known as immune checkpoint blockade (ICB), has been proposed as approach to improve outcomes in patients with intermediate stage (Barcelona Clinic Liver Cancer, BCLC B) or advanced stage (BCLC C) hepatocellular carcinoma (HCC). Unfortunately, only a select patients can benefit from ICB. Hence, biomarkers that can predict the success and survival of treatment are still necessary.Patients and Methods: Between 2018 to 2021, 132 patients received ICB treatment for intermediate or advanced stage HCC. Based on the early kinetics of C-reactive protein (CRP), the patients were classified into three groups. The study endpoints were progression-free survival (PFS) and overall survival (OS).Results: Our findings support the predictive power of early CRP kinetics in determining immunotherapy response for intermediate or advanced HCC. Objective response rates (ORR) were found in 41.2% of CRP flare-responders, 13.3% of CRP responders, and 3.5% of CRP non-responders (p< 0.001). Disease control rates (DCR) in the three groups were substantially different (p< 0.001). The improved PFS and OS were strongly correlated with the early kinetics of CRP. Compared to CRP non-responders, CRP responders, especially CRP flare-responders, had significantly longer PFS (median PFS: CRP flare-responders: 11.6 months vs CRP responders: 5.2 months vs CRP non-responders: 2.3 months, p< 0.001).Conclusion: The CRP flare response robustly predicts the immunotherapy response and outcomes in patients with HCC. Early CRP kinetics may be an inexpensive, easily implemented and non-invasive biomarker to anticipate response to ICB therapy in intermediate or advanced HCC, with the potential to optimize treatment monitoring.Keywords: hepatocellular carcinoma, C‐reactive protein kinetics, CRP flare response, immune checkpoint blockade, biomarker, immunotherapy
