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

Pei, Fengyun1; Wu, Jingjing1; Zhao, Yandong2; He, Wan3; Yao, Qijun1; Huang, Meijin1; Huang, Jun1,4,5

2023-03-01

10.1016/j.clcc.2022.11.004

CLINICAL COLORECTAL CANCER   Impact Factor & Quartile

1533-0028

1938-0674

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.

Colorectal cancer dMMR MSI-H PD-1 blockade Neoadjuvant immunotherapy Local advanced

SCI

English

Others

National Natural Science Foundation of C hina[81972885] ; 1010 project of the Sixth Affiliated Hospital of Sun Yat-sen University[1010CG (2020) -20]

Oncology

Oncology

WOS:000957345000001

CIG MEDIA GROUP, LP

Web of Science

1.Sun Yat Sen Univ, Affiliated Hosp 6, Dept Colorectal Surg, Yuan Cun Er Heng Rd 26, Guangzhou 510655, Peoples R China
2.Sun Yat Sen Univ, Affiliated Hosp 6, Dept Pathol, Guangzhou, Peoples R China
3.Jinan Univ, Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1, Shenzhen, Guangdong, Peoples R China
4.Sun Yat Sen Univ, Affiliated Hosp 6, Guangdong Prov Key Lab Colorectal & Pelv Floor Dis, Guangzhou, Peoples R China
5.Guangdong Inst Gastroenterol, Guangzhou, Peoples R China

Pei, Fengyun,Wu, Jingjing,Zhao, Yandong,et al. Single-Agent Neoadjuvant Immunotherapy With a PD-1 Antibody in Locally Advanced Mismatch Repair-Deficient or Microsatellite Instability-High Colorectal Cancer[J]. CLINICAL COLORECTAL CANCER,2023,22(1).

Pei, Fengyun.,Wu, Jingjing.,Zhao, Yandong.,He, Wan.,Yao, Qijun.,...&Huang, Jun.(2023).Single-Agent Neoadjuvant Immunotherapy With a PD-1 Antibody in Locally Advanced Mismatch Repair-Deficient or Microsatellite Instability-High Colorectal Cancer.CLINICAL COLORECTAL CANCER,22(1).

Pei, Fengyun,et al."Single-Agent Neoadjuvant Immunotherapy With a PD-1 Antibody in Locally Advanced Mismatch Repair-Deficient or Microsatellite Instability-High Colorectal Cancer".CLINICAL COLORECTAL CANCER 22.1(2023).