Efficacy and safety profile of dMMR/MSI immunotherapy in metastatic colorectal cancer in real-world clinical practice

Abstract

Introduction. Deficiency of the mismatch repair system (dMMR) and microsatellite instability (MSI) occur in only 4–5% of patients with metastatic colorectal cancer (mCRC), but this molecular subgroup is characterized by high sensitivity to immune checkpoint inhibitors. Data on the efficacy and safety of such therapy in the Russian population are limited, making this study relevant for real-world clinical practice. Aim. Evaluation of the efficacy and safety of immunotherapy in patients with mCRC and MSI. Materials and methods. This retrospective, multicenter, multicohort, non-randomized study included 74 patients (36 men and 38 women) aged 19 to 85 years. The median follow-up was 41.2 months. Patients received monotherapy (pembrolizumab, nivolumab) or a combination (nivolumab and ipilimumab). An objective tumor response to treatment was defined as partial or complete tumor regression. Tumor response to treatment was determined using iRECIST criteria. Results. Progression-free survival in patients with MSI-positive mCRC was 45.53 months (95% CI: 12.26 – ∞ months) in the monoimmunotherapy group and was not achieved in the combination therapy group, p < 0.05. Overall survival was 45.76 months (95% CI: 25.78 – ∞ months) in the monoimmunotherapy group and was not achieved in the combination therapy group, p < 0.05. Objective response was achieved in 18 (46%) patients in the monoimmunotherapy group and in 19 (54.30%) patients in the combination therapy group. Immune-mediated adverse events of grade 3–4 were observed only in 11 (11.86%) patients. Conclusion. The use of immunotherapy in mCRC with MSI allows achieving high rates of objective response and disease control (50% and 75.7%, respectively) with a favorable safety profile (severe complications – 11.86%).