Single-Agent Neoadjuvant Immunotherapy With a PD-1 Antibody in Locally Advanced Mismatch Repair-Deficient or Microsatellite Instability-High Colorectal Cancer
Single-Agent Neoadjuvant Immunotherapy With a PD-1 Antibody in Locally Advanced Mismatch Repair-Deficient or Microsatellite Instability-High Colorectal Cancer
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DOI：
10.1016/j.clcc.2022.11.004
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发表时间：
2023-03-17
影响因子：
3.4
通讯作者：
Huang, Jun
中科院分区：
文献类型：
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作者：
Pei, Fengyun;Wu, Jingjing;Huang, Jun
新辅助PD-1阻断免疫治疗局部晚期dMMR/MSI-H CRC的安全性和有效性尚不清楚。11例局部晚期dMMR/MSI-H型结直肠癌患者在腹腔镜根治性切除术前接受6次辛替单抗（200 mg/注射，每3周）注射。90.9%的患者病理完全缓解（pCR）。单药新辅助PD-1抗体免疫治疗局部晚期dMMR/MSI-H CRC安全有效。背景：PD-1阻断已被推荐作为不可切除或转移性错配修复缺陷/微卫星不稳定性高（dMMR/MSI-H）结直肠癌（CRC）的一线治疗。然而，新辅助PD-1阻断免疫治疗局部晚期dMMR/MSI-H CRC的安全性和有效性尚不清楚。患者和方法：2020年6月至2022年6月，在中山大学第六附属医院（中国广州）接受治疗的11例本地晚期dMMR/MSI-H CRC患者入组。所有患者在腹腔镜根治性切除术前均接受6次sintilmab （Innovent， LTD）注射（200mg /注射，每3周）。回顾性分析患者的临床及病理资料。结果：所有患者的dMMR均经免疫组化证实。然而，聚合酶链反应（PCR）或新一代测序仅为90.9%（10/11）的患者证实MSI-H， 1例患者为微卫星稳定型（MSS）疾病。经6次新辅助抗pd -1治疗后，90.9%（10/11）的患者（确诊为dMMR和MSI-H病的患者）达到病理完全缓解（pCR）。另一例获得主要病理反应，肿瘤残留< 1%的患者有dMMR，但有MSS疾病。未发生3级或以上免疫治疗相关不良事件[不良事件通用术语Crⅰa；5.0版本)。总体而言，72.7%（8/11）的患者发生1-2级免疫治疗相关不良事件。术后30天内无手术死亡及并发症发生。结论：单药新辅助PD-1抗体免疫治疗局部晚期dMMR/MSI-H结直肠癌安全有效。dMMR/MSI- h结直肠癌患者在免疫治疗前需要免疫组织化学和新一代测序或PCR双重确认MMR和MSI状态。本研究中使用的免疫治疗方案值得在II期和III期临床研究中进一步验证。
The safety and efficacy of neoadjuvant PD-1 blockade immunotherapy for locally advanced dMMR/MSI-H CRC remain unclear. Eleven locally advanced dMMR/MSI-H CRC patients received 6 sintilimab (Innovent, LTD) injec-tions (200 mg/injection, every 3 weeks) before radical laparoscopic resection. 90.9% of the patients achieved pathological complete response (pCR). Single-agent neoadjuvant PD-1 antibody immunotherapy was safe and effective in locally advanced dMMR/MSI-H CRC. Background: PD-1 blockade has been recommended as first-line therapy for nonresectable or metastatic mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC). However, the safety and efficacy of neoadjuvant PD-1 blockade immunotherapy for locally advanced dMMR/MSI-H CRC remain unclear. Patients and Methods: From June 2020 to June 2022, 11 locally advanced dMMR/MSI-H CRC patients treated at the Sixth Affili-ated Hospital of Sun Yat-sen University (Guangzhou, China) were enrolled. All patients received 6 sintilimab (Innovent, LTD) injections (200 mg/injection, every 3 weeks) before radical laparoscopic resection. The patient clinical and patho-logical data were analyzed retrospectively. Results: dMMR was confirmed by immunohistochemistry for all patients. However, polymerase chain reaction (PCR) or next-generation sequencing confirmed MSI-H for only 90.9% (10/11) of the patients, while 1 patient had microsatellite stable (MSS) disease. After 6 injections of neoadjuvant anti-PD-1 therapy, 90.9% (10/11) of the patients (those confirmed to have dMMR and MSI-H disease) achieved pathological complete response (pCR). The other patient, who achieved major pathological response with residual tumor < 1%, had dMMR but MSS disease. No grade 3 or above immunotherapy-related adverse events occurred [Common Terminology Cr iter ia for Adverse Events ; version 5.0]. Overall, 72.7% (8/11) of the patients had grade 1-2 immunotherapy-related adverse events . No operational mortality or complications occurred within 30 days after surgery. Conclusion: Single -agent neoadjuvant PD-1 antibody immunotherapy was safe and effective in locally advanced dMMR/MSI-H CRC. Dual confirmation of MMR and MSI status by immunohistochemistry and next-generation sequencing or PCR is necessary for dMMR/MSI-H CRC patients before immunotherapy. The immunotherapy regimen used in this study deserves further validation in phase II and III clinical studies.