Zhang Jinli, Yang Lu, Kong Fanwei, Wu Di, Hu Baoru, Yang Jie, He Jiaxin, Liu Lei
Department of Internal Medicine, Harbin Medical University Cancer Hospital, Harbin, China.
The Genetic Analysis Department, YuceBio Technology Co., Ltd., Shenzhen, China.
Front Med (Lausanne). 2023 May 4;10:1051034. doi: 10.3389/fmed.2023.1051034. eCollection 2023.
Approximately 5% of advanced colorectal carcinomas (CRCs) and 12-15% of early CRCs are microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) tumors. Nowadays, PD-L1 inhibitors or combined CTLA4 inhibitors are the major strategies for advanced or metastatic MSI-H colorectal cancer, but some people still show drug resistance or progression. Combined immunotherapy has been shown to expand the benefit population in non-small-cell lung carcinoma (NSCLC), hepatocellular carcinoma (HCC), and other tumors while reducing the incidence of hyper-progression disease (HPD). Nevertheless, advanced CRC with MSI-H remains rare. In this article, we describe a case of an elder patient with MSI-H advanced CRC carrying MDM4 amplification and DNMT3A co-mutation who responded to sintilimab plus bevacizumab and chemotherapy as the first-line treatment without obvious immune-related toxicity. Our case provides a new treatment option for MSI-H CRC with multiple risk factors of HPD and highlights the importance of predictive biomarkers in personalized immunotherapy.
约5%的晚期结直肠癌（CRC）和12 - 15%的早期CRC是微卫星高度不稳定（MSI-H）或错配修复缺陷（dMMR）肿瘤。如今，PD-L1抑制剂或联合CTLA4抑制剂是晚期或转移性MSI-H结直肠癌的主要治疗策略，但仍有一些人表现出耐药或疾病进展。联合免疫疗法已被证明可扩大非小细胞肺癌（NSCLC）、肝细胞癌（HCC）和其他肿瘤的受益人群，同时降低超进展性疾病（HPD）的发生率。然而，MSI-H的晚期CRC仍然罕见。在本文中，我们描述了一例携带MDM4扩增和DNMT3A共突变的MSI-H晚期CRC老年患者，该患者一线接受信迪利单抗联合贝伐单抗及化疗治疗，疗效良好且无明显免疫相关毒性。我们的病例为具有HPD多种危险因素的MSI-H CRC提供了一种新的治疗选择，并突出了预测性生物标志物在个性化免疫治疗中的重要性。
