Neoadjuvant Immunotherapy With Ipilimumab Plus Nivolumab in Mismatch Repair Deficient/Microsatellite Instability-High...

Although ipilimumab plus nivolumab have significantly improved the survival of metastatic colorectal cancer (CRC) with mismatch repair deficient (dMMR) /microsatellite instability-high (MSI-H), the data on neoadjuvant setting is limited.

We enrolled 11 patients with advanced dMMR/MSI-H CRC. 10 patients were locally advanced and 1 was metastatic. Ten patients were treated with 1 dose of ipilimumab (1 mg/kg) and 2 doses of nivolumab (3 mg/kg), and 1 patient was treated with 1 dose of ipilimumab (1 mg/kg) and 2 doses of nivolumab (3 mg/kg) with 2 cycles. All the patients underwent surgery after immunotherapy. The aim of the study was to evaluate the safety and short-term efficacy of this strategy.

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, 1 achieved a radiological noncomplete response after treatment with 1 dose of ipilimumab (1 mg/kg) and 2 doses of nivolumab (3 mg/kg), so another cycle of treatment with 1 dose of ipilimumab (1 mg/kg) and 2 doses of nivolumab (3 mg/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.

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.