Immune checkpoint inhibitors in digestive tumors with mismatch repair deficiency or microsatellite instability (dMMR/MSI-H): Effectiveness, safety, and prognostic factors in real-world practice.

Abstract

202 Background: ICIs have shown durable responses in dMMR/MSI-H digestive tumors in phase II-III clinical trials. The aim of this study is to evaluate the efficacy, safety and prognostic factors in the context of real-world practice. Methods: We conducted a retrospective multicenter observational study of patients with dMMR/MSI-H digestive tumors treated with ICIs in routine clinical practice across seven university hospitals in northwest Spain. We analyzed clinicopathological characteristics, treatment response data, efficacy, and adverse events. Results: A total of 122 patients treated with ICIs between November 2015 and February 2024 were included. The median age was 70.4 years (range 29-89), and 52.4% were male. The most frequent origin was colorectal (54.9%; 67.2% located in the right colon and 37.3% BRAF V600mt), followed by gastroesophageal adenocarcinoma (34.4%). 16.4% had >3 metastatic sites (including 30.3% liver metastases and 44.3% peritoneal metastases). Baseline performance status (ECOG PS) was 0/1/2 in 21.7%/58.7%/19.8%, respectively. 39.3% had received one prior line of treatment. 92.6% received pembrolizumab monotherapy. The objective response rate (ORR) was 77.7% (including 31.3% complete response, 46.4% partial response, 13.4% stable disease, and 8.9% progressive disease), and the disease control rate (DCR) was 90.1%. Median overall survival (OS) was 53.2 months (95% CI: 42.6 – 63.7 months), and progression-free survival (PFS) was 46 months (95% CI: 30.6 – 61.4 months). The most common grade 3-4 treatment-related adverse events included nephritis (4.0%), hepatitis (3.3%), asthenia (2.5%), and pneumonitis (1.6%). 81.1% of patients discontinued treatment (including 24.6% due to progression, 21.3% after completing 2 years of treatment, and 14.8% due to toxicity). Potential prognostic factors identified in univariate analysis included ECOG PS, primary tumor resection, number of metastatic sites, and best treatment response. In multivariate analysis, a significant association was confirmed between ECOG PS, the presence of liver metastases, and best response to treatment with ICIs and overall survival. Conclusions: Our series confirms the efficacy and safety of ICIs in dMMR/MSI-H digestive tumors in routine clinical practice. The identified prognostic factors may be useful for identifying patients who could benefit the most from ICI treatment.