Efficacy, Safety, and Survival Outcomes of Immune Checkpoint Inhibitors in Patients with Mismatch Repair-Deficient Colorectal Cancer: A Retrospective, Multicenter Study

<b>Background</b>: Microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) colorectal cancer (CRC) accounts for approximately 5% of metastatic CRC cases. Immune checkpoint inhibitors (ICIs) are the standard of care based on pivotal clinical trials; however, real-world data, particularly from low-resource countries, remain scarce, and prognostic factors are not yet fully defined. Therefore, we evaluated the efficacy and the safety of ICIs in a multi-center cohort. <b>Methods</b>: This multi-center retrospective study included 45 patients treated with ICIs across six oncology centers in Türkiye between June 2017 and December 2024. Patients received either anti-PD-1/PD-L1 monotherapy or anti-CTLA-4-based combination therapy. Key clinical variables and 1-, 2-, and 3-year OS and PFS outcomes were systematically collected. <b>Results</b>: The median age was 61 years, and most patients (75.6%) received ICIs in later treatment lines. After a median follow-up of 24.1 months, median OS and PFS were not reached. The estimated 1-, 2-, and 3-year OS rates were 82%, 76.1%, and 76.1%; PFS rates were 75.6%, 67.5%, and 67.5%, respectively. In multivariate analysis, an ECOG < 1 (HR: 0.072; 95% CI: 0.012-0.453; <i>p</i> = 0.005), a metastatic burden of fewer than two sites (HR: 0.211; 95% CI: 0.052-0.860; <i>p</i> = 0.030), and absence of antibiotic exposure within one month prior to immunotherapy initiation (HR: 0.145; 95% CI: 0.034-0.614; <i>p</i> = 0.009) were independently associated with improved overall survival. For PFS, ECOG < 1 (HR: 0.172; 95% CI: 0.052-0.573; <i>p</i> = 0.004), a metastatic burden of fewer than two sites (HR: 0.248; 95% CI: 0.078-0.788; <i>p</i> = 0.018), and no recent antibiotic exposure (HR: 0.209; 95% CI: 0.064-0.687; <i>p</i> = 0.010) remained independent predictors of prolonged survival. <b>Conclusions</b>: We observed overall survival outcomes similar to those reported in phase III clinical trials of immunotherapy in MSI-H/dMMR colorectal cancer, despite a substantial proportion of patients receiving immunotherapy in later lines of treatment. These findings support immune checkpoint inhibitors as the standard of care for MSI-H/dMMR metastatic colorectal cancer and emphasize the importance of improving access to immunotherapy, particularly in low-resource settings.