POLE-Mutant Colon Cancer Treated with PD-1 Blockade Showing Clearance of Circulating Tumor DNA and Prolonged Disease-Free Interval

Colon cancer with high microsatellite instability is characterized by a high tumor mutational burden and responds well to immunotherapy. Mutations in polymerase e, a DNA polymerase involved in DNA replication and repair, are also associated with an ultra-mutated phenotype. We describe a case where a patient with POLE-mutated and hypermutated recurrent colon cancer was treated with pembrolizumab. Treatment with immunotherapy in this patient also led to the clearance of circulating tumor DNA (ctDNA). ctDNA is beginning to emerge as a marker for minimal residual disease in many solid malignancies, including colon cancer. Its clearance with treatment suggests that the selection of pembrolizumab on the basis of identifying a POLE mutation on next-generation sequencing may increase disease-free survival in this patient.

Automated summary

Colon cancer with high microsatellite instability responds well to immunotherapy, especially in cases with POLE mutations. We present a case of a POLE-mutated recurrent colon cancer patient treated with pembrolizumab, which resulted in the clearance of circulating tumor DNA. This suggests that using next-generation sequencing to identify POLE mutations and selecting pembrolizumab may improve disease-free survival in similar patients.