Good Tumor Response to Chemoradioimmunotherapy in dMMR/MSI-H Advanced Colorectal Cancer: A Case Series

Immune checkpoint blockade has led to a significant improvement of patient survival in metastatic colorectal cancer (CRC) with DNA mismatch repair-deficiency (dMMR)/microsatellite instability-high (MSI-H). However, not all these patients are sensitive to monoimmunotherapy. We firstly presented a case series of advanced dMMR/MSI-H CRCs treating with PD-1 inhibitor-based chemoradioimmunotherapy (CRIT).We assessed the short-term efficacy and safety of CRIT in advanced dMMR/MSI-H CRCs, and also did next-generation sequencing (NGS) assays.Our analysis included five advanced dMMR/MSI-H CRCs who have received toripalimab-based CRIT. Toripalimab was given 240mg every three weeks, and the radiation dose was 45-50 gray in 25 fractions. Chemotherapy regimens consisted of CAPOX in three patients, capecitabine in one patient, and mFOLFOX6 in one patient. Initially, two patients displayed complete response (CR), and three patients achieved partial response (PR) on imaging findings. Afterwards, one PR patient was confirmed pathological complete response after surgery, leading to three CR cases in total. Hematological toxicity was the most common adverse effect, and only two patients developed mild immune-related adverse effects besides. All the treatment-related adverse events were under control. Based on the NGS results, the median intratumor heterogeneity was 0.19 (range 0-0.957), which was less in CR patients than PR patients (P = 0.019). Genetic mutations at DNA damage repair genes and the JAK1 gene were also observed.For advanced dMMR/MSI-H CRC, anti-PD-1 based CRIT is effective and safe. Further studies are required to better clarify the potential role and mechanism of CRIT as a viable therapeutic strategy in this population.