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

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

Caroline Drumm1, Maeve O’Neill1, Brian Mehigan1,2, John Larkin1,2, Paul McCormick1,2, Grainne O’Kane1,2, David Gallagher1,2, Michael Eamonn Kelly1,2

1Department of Surgery, St. James’s Hospital, Dublin, Ireland; 2Trinity St. James’s Cancer Institute, Dublin, Ireland

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.

Keywords: Colorectal cancer (CRC); immune checkpoint inhibitors (ICIs); immunotherapy; mismatch repair (MMR); unresectable

Acknowledgments

None.

Footnote

Funding: None.

Conflicts of Interest: The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

doi: 10.21037/map-25-ab138
Cite this abstract as: Drumm C, O’Neill M, Mehigan B, Larkin J, McCormick P, O’Kane G, Gallagher D, Kelly ME. AB138. SOH25_AB_078. The use of neoadjuvant immunotherapy for mismatch repair deficient (dMMR) locally advanced and metastatic colorectal cancer (CRC). Mesentery Peritoneum 2025;9:AB138.

Article Options

Download Citation

Share