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.

中文翻译：

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伊匹单抗联合纳武单抗治疗错配修复缺陷/微卫星不稳定性高结直肠癌的新辅助免疫治疗：病例系列初步报告

尽管伊匹单抗联合纳武单抗显着改善了错配修复缺陷（dMMR）/微卫星不稳定性高（MSI-H）的转移性结直肠癌（CRC）的生存率，但新辅助治疗的数据有限。我们招募了 11 名晚期 dMMR/MSI-H CRC 患者。10 例患者为局部晚期，1 例为转移。10 名患者接受 1 剂伊匹单抗 (1 mg/kg) 和 2 剂纳武单抗 (3 mg/kg) 治疗，1 名患者接受 1 剂伊匹单抗 (1 mg/kg) 和 2 剂纳武单抗 (3 mg/kg) 治疗。 mg/kg），2个周期。所有患者均在免疫治疗后接受手术。该研究的目的是评估该策略的安全性和短期疗效。在 11/11 (100%) dMMR/MSI-H 肿瘤中观察到病理缓解，其中 9/11 (81.8%) 实现完全缓解。在这9例完全缓解的病例中，有1例在接受1剂ipilimumab（1 mg/kg）和2剂nivolumab（3 mg/kg）治疗后达到放射学不完全缓解，因此再接受1剂ipilimumab治疗（给予 1 毫克/公斤）和 2 剂纳武单抗（3 毫克/公斤），然后进行手术。术后病理评估为完全缓解。7 名患者（63.6%）出现 I/II 级不良事件。没有患者出现 III/IV 级不良事件或术后并发症。在晚期 dMMR/MSI-H CRC 中，伊匹单抗加纳武单抗的新辅助免疫治疗可诱导肿瘤消退，并产生重大临床和病理反应。值得注意的是，患者对新辅助免疫治疗没有达到完全缓解，额外的新辅助免疫治疗可能会带来好处。需要进一步的研究来评估该策略的长期有效性。