Single-Agent Neoadjuvant Immunotherapy With a PD-1 Antibody in Locally Advanced Mismatch Repair-Deficient or Microsatellite Instability-High Colorectal Cancer

• Published in: Clinical colorectal cancer 2023-03, Vol.22 (1), p.85-91
• Main Authors: Pei, Fengyun, Wu, Jingjing, Zhao, Yandong, He, Wan, Yao, Qijun, Huang, Meijin, Huang, Jun
• Format: Article
• Language: English
• Subjects: Colonic Neoplasms; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; dMMR/MSI-H; DNA Mismatch Repair - genetics; Humans; Immunotherapy - adverse effects; Local advanced; Microsatellite Instability; Neoadjuvant immunotherapy; Neoadjuvant Therapy; PD-1 blockade; Retrospective Studies
• ISSN: 1533-0028; 1938-0674
• DOI: 10.1016/j.clcc.2022.11.004

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) injections (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. 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. From June 2020 to June 2022, 11 locally advanced dMMR/MSI-H CRC patients treated at the Sixth Affiliated 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 pathological data were analyzed retrospectively. 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