AB138. SOH25_AB_078. The use of neoadjuvant immunotherapy for mismatch repair deficient (dMMR) locally advanced and metastatic colorectal cancer (CRC)

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Background: Mismatch repair (MMR) plays a vital role in the regulation of cell cycle checkpoints to maintain genomic stability. MMR status can serve as a tumour biomarker to predict response to immune checkpoint inhibitors (ICIs). Methods: This retrospective study evaluated outcomes for patients with initially unresectable locally advanced or oligometastatic MMR deficient (dMMR) colorectal cancer (CRC) receiving neoadjuvant ICIs. A PD-1 inhibitor was administered 6-weekly for up to 2 years, ceasing upon disease progression or sufficient downstaging to permit curative resection. Results: Between October 2022 and September 2024, 10 patients with unresectable dMMR CRC (one stage 2, seven stage 3, two stage 4) underwent neoadjuvant treatment with ICIs. Over a median 12.5-month follow-up period, nine of 10 patients demonstrated significant downstaging of disease, rendering them suitable for potentially curative resection. The remaining patient is awaiting re-imaging. To date, 3 of 10 patients (33%) have achieved complete curative response. Regarding treatment-related adverse events, 2 patients (20%) experienced grade 3–4 events, including strictures and tumour perforation. Conclusions: Neoadjuvant ICIs show promising outcomes for locally advanced or metastatic dMMR CRC, with excellent response rates and downstaging potential. This emphasizes the importance of assessing MMR status for all CRC patients. In cases of unresectable CRC, initial management with ICI can allow for progression to potentially curative resection, however deep responses may cause local complication. Ultimately, further large-sample, high quality data is required, but early results are promising.

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