Outcomes with immunotherapy between Lynch syndrome vs non-Lynch syndrome microsatellite instability-high colorectal cancer.

• DOI: 10.1200/jco.2024.42.3_suppl.175
• Publication Date: 2024-01-22T21:12:58Z
• Authors: Cody Eslinger; Alyssa McGary; Daniel Walden; Oluwadunni Eunice...; Daniel H. Ahn; Bassam Bassam Sonbol; Tanios S. Bekaii-...; Mojun Zhu; Joleen M. Hubbard; Christina Wu
• Keywords: Microsatellite Instability; Lynch Syndrome; MLH1; MSH2; PMS2; MSH6

175 Background: Alterations to mismatch repair (MMR) genes such as MLH1, MSH2, MSH6, and PMS2, can lead microsatellite instability-high (MSI-H) tumors. MMR mutations be inherited in Lynch syndrome (LS) but also a result of de novo alterations resulting MSI-H malignancies. Treatment with immune checkpoint inhibitors (ICIs) have been shown improve survival patients (pts) compared systemic chemotherapy. However, there is paucity information the literature respect outcomes pts germline vs somatic colorectal cancer (CRC). Furthermore, presence underlying BRAF mutation confers resistance chemotherapy CRC, however data regarding immunotherapy CRC lacking. Methods: Pt records from Mayo Clinic (AZ, MN, FL) between 2008-2023 denoted were included for retrospective review. demographics, treatment courses, genomic profiles collected. Overall (OS) progression-free (PFS) estimated using Kaplan-Meier method. Outcome differences sub-groups accessed log rank test univariate analyses assessed Cox-regression. Results: A total 81 pt identified (n = 18 LS, n 63 non-LS). Stage IV disease was found 28% LS 59% non-LS at diagnosis. Pembrolizumab most common ICI selected metastatic both (65% 94%) median duration each group 11.7 8.8 months. There no OS or PFS any stage non-LS. Median all 82 For patients, 44 months, 19 Interestingly, treated immunotherapy, tumors that harbored V600E 21) wild type 20) had significantly lower 113 months (HR 2.69, p 0.043) well 12 95 2.48, 0.041). Conclusions: In this study, we patient ICIs similar vs. CRC. The an associated mutation, which occurs conferred worse outcomes.