Neoadjuvant immunotherapy with ipilimumab plus nivolumab in mismatch repair deficients/microsatellite instability-high colorectal cancer: a preliminary report of case series

Background Although ipilimumab plus nivolumab have significantly improved the survival of metastatic colorectal cancer (CRC) with mismatch repair deficients (dMMR) /microsatellite instability-high (MSI-H), the data on neoadjuvant setting is limited. Patients and Methods We enrolled 11 patients with advanced dMMR/MSI-H CRC. 10 patients were locally advanced and one was metastatic. 10 patients were treated with one dose of ipilimumab (1mg/kg) and two doses of nivolumab (3mg/kg), and one patient was treated with one dose of ipilimumab (1mg/kg) and two doses of nivolumab (3mg/kg) with two cycles. All the patients underwent sugery after immunotherapy. The aim of the study was to evaluate the safety and short-term efficacy of this strategy. Results Pathologic responses were observed in 11/11 (100%) dMMR/MSI-H tumors, with 9/11 (81.8%) achieving complete responses. Among these 9 cases with complete responses, one achieved a radiological non-complete response after treatment with one dose of ipilimumab (1mg/kg) and two doses of nivolumab (3mg/kg), so another cycle of treatment with one dose of ipilimumab (1mg/kg) and two doses of nivolumab (3mg/kg) was administered, followed by surgery. The postoperative pathological evaluation was a complete response. Seven patients (63.6%) developed grade I/II adverse events. No patients developed grade III/IV adverse events or postoperative complications. Conclusion Neoadjuvant immunotherapy with ipilimumab plus nivolumab induced tumor regression with a major clinical and pathological response in advanced dMMR/MSI-H CRC. Notably, patients do not achieve a complete response to neoadjuvant immunotherapy, additional neoadjuvant immunotherapy may offer benefits. Further research is needed to assess the long-term efficacy of this strategy. Micro Abstract The safety and efficacy of neoadjuvant immunotherapy with ipilimumab plus nivolumab for locally advanced mismatch repair deficients/microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC) remain unclear. 11 locally advanced dMMR/MSI-H CRC patients received ipilimumab and nivolumab before surgery. 9 (81.8%) patients achieved pathological complete response (pCR). Neoadjuvant immunotherapy with ipilimumab plus nivolumab was safe and effective in locally advanced dMMR/MSI-H CRC.