Efficacy of PD-1 inhibitors for colorectal cancer and polyps in patients with Lynch syndrome

e15521 Background: Programmed death-1 (PD-1) inhibitor is effective for colorectal cancer (CRC) with deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H). We aimed to explore its effects on CRCs and colonic polyps in Lynch syndrome (LS) patients. Methods: LS patients with CRC who had evaluable tumors and received ≥2 cycles of PD-1 inhibitors were included. PD-1 inhibitors were given as a monotherapy or in combination with other therapies including anti cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) treatment, radiotherapy, chemotherapy, and targeted therapy. Correlations of treatment responses with clinicopathological characteristics and genomic profiles were analyzed. Results: A total of 75 LS patients were included, with a median age of 39 years. The median duration of follow-up was 27 months (range, 3 to 71). The objective response rate (ORR) was 70.7%, including 28.0% (n = 21) complete responses (CRs) and 42.7% (n = 32) partial responses (PRs). Three cases of LS CRCs displaying pMMR/MSS or discordant MMR/MSI status were not responsive even with a high tumor mutation burden (TMB). Mucinous/signet-ring cell differentiation was associated with a lower ORR ( P= 0.013). The 3-year OS and PFS was 91.2% and 81.0%, respectively. Colorectal polyp/adenoma was detected in 26 patients during surveillance. Seven adenomas disappeared after treatment and their maximum diameters were all larger than 7mm. Conclusions: PD-1 inhibitors are highly effective for dMMR/MSI-H LS CRCs, but not for pMMR/MSS LS CRCs or those displaying discordant MMR/MSI status or mucinous/signet-ring cell CRC. Some of the large LS adenomas may also be sensitive to anti-PD-1 treatment.