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POLE-Mutant Colon Cancer Treated with PD-1 Blockade Showing Clearance of Circulating Tumor DNA and Prolonged
Mihir Bikhchandani1, Farin Amersi2, Andrew Hendifar3
1Department of Hematology and Oncology, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA 90027, USA.
Abstract:
Colon cancer with high microsatellite instability is characterized by a high tumor mutational burden and responds well to immunotherapy. Mutations in polymerase ɛ, 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.
Insights
High microsatellite instability colon cancer, characterized by a POLE mutation, responded well to immunotherapy. Pembrolizumab treatment led to the clearance of circulating tumor DNA, suggesting potential for increased disease-free survival.
Area of Science:
- Oncology
- Genetics
- Immunotherapy
Background:
- Colon cancer with high microsatellite instability (MSI-H) exhibits a high tumor mutational burden (TMB) and typically responds well to immunotherapy.
- Mutations in DNA polymerase epsilon (POLE) are linked to an ultra-mutated phenotype, similar to MSI-H.
- Circulating tumor DNA (ctDNA) is an emerging biomarker for minimal residual disease (MRD) in various solid tumors, including colon cancer.
Observation:
- A case study involving a patient with recurrent colon cancer harboring POLE mutations and a hypermutated phenotype was treated with pembrolizumab.
- The patient received pembrolizumab, a type of immunotherapy.
- Following treatment, a significant reduction in circulating tumor DNA (ctDNA) was observed.
Findings:
- The patient with POLE-mutated, hypermutated colon cancer experienced clearance of circulating tumor DNA (ctDNA) after pembrolizumab treatment.
- This suggests a positive response to immunotherapy in this specific genetic subtype of colon cancer.
- The observed ctDNA clearance indicates a potential reduction in minimal residual disease.
Implications:
- Identifying POLE mutations via next-generation sequencing may guide the selection of pembrolizumab for specific colon cancer patients.
- This targeted immunotherapy approach could potentially improve disease-free survival rates.
- Further research into ctDNA dynamics and POLE mutations in colon cancer immunotherapy is warranted.
