Serum Concentration of CD137 and Tumor Infiltration by M1 Macrophages Predict the Response to Sintilimab plus Bevacizumab Biosimilar in Advanced Hepatocellular Carcinoma Patients

作者：Wen Zhang, Caifeng Gong, Xuenan Peng, Xinyu Bi, Yongkun Sun, Jian‐Guo Zhou, Fan Wu, Huiying Zeng, Yan Wang, Hui Zhou, Hong Zhao, Jianqiang Cai, Aiping Zhou · 发表于：Clinical Cancer Research · 年份：2022 · DOI：10.1158/1078-0432.ccr-21-3972 · 被引用次数：56 · 研究领域：Cancer Immunotherapy and Biomarkers、Immune cells in cancer、Colorectal Cancer Treatments and Studies

PURPOSE: This study aimed to investigate the biomarkers of sintilimab (anti-PD-1) plus IBI305 (a bevacizumab biosimilar) in advanced hepatocellular carcinoma (HCC), as well as their safety and efficacy. PATIENTS AND METHODS: A total of 50 patients with advanced HCC received sintilimab (200 mg) plus IBI305 (7.5 or 15 mg/kg), treated every 3 weeks in a phase Ib clinical study. We performed baseline serum cytokine analysis using bead-based multiplex immunoassay and multiplex immunofluorescence on tissue specimens to discover novel biomarkers of response to VEGF/PD-1 combination therapy in HCC. RESULTS: The overall response rate was 34.0% (17/50). The median progression-free survival (PFS) and the median overall survival were 10.5 and 20.2 months, respectively. The incidence of grade 3 to 5 adverse events was lower in the 7.5 mg/kg (13.8%) than in the 15 mg/kg (28.6%) dose groups. Biomarker analysis showed that the serum CD137 concentration was significantly higher in patients with clinical benefit (CB) than in those without CB (median, 32.8 pg/mL vs. 19.8 pg/mL, P = 0.034). A markedly longer PFS was observed in patients with high CD137 concentrations compared with those with low concentrations (median, 14.2 months vs. 4.1 months, P = 0.001). The higher density of M1 macrophages (CD68+CD163-) in the stroma was also associated with higher efficacy (P = 0.033) and a longer PFS (P = 0.024). CONCLUSIONS: Sintilimab plus IBI305 was well tolerated and was effective therapy for advanced...