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A rare case of sporadic mismatch repair deficient pancreatic ductal adenocarcinoma that responded to ipilimumab and nivolumab combination treatment: case report.
Journal of Gastrointestinal Oncology 2023 Februrary 29
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignant disease with a poor prognosis. Despite high efficacy in multiple cancers, immunotherapy has had very little success in treating PDAC due to unfavorable characteristics such as low tumor mutational burden (TMB), low microsatellite instability (MSI), and non-immunogenic tumor microenvironment. Recently, however, there have been reports of rare PDAC cases with high TMB and DNA mismatch repair deficiency (dMMR) that have demonstrated positive response to immunotherapy. All these cases have also presented with Lynch Syndrome, or germline mutations in MMR genes.
CASE DESCRIPTION: Here, we report a 57-year-old male with stage IV PDAC whose tumor profile revealed high TMB, high MSI, and dMMR, but no germline mutations in genes associated with hereditary cancers including those associated with Lynch Syndrome. After a series of ineffective treatments, the patient showed positive response to combined ipilimumab and nivolumab immunotherapy. To our knowledge, this is the first report of an advanced PDAC case with sporadic dMMR, high TMB, and no Lynch Syndrome having a good response to immunotherapy.
CONCLUSIONS: This case further supports TMB and high MSI/dMMR being possible biomarkers for immunotherapy of PDAC as well as highlights the importance of both germline and somatic testing of patients with PDAC.
CASE DESCRIPTION: Here, we report a 57-year-old male with stage IV PDAC whose tumor profile revealed high TMB, high MSI, and dMMR, but no germline mutations in genes associated with hereditary cancers including those associated with Lynch Syndrome. After a series of ineffective treatments, the patient showed positive response to combined ipilimumab and nivolumab immunotherapy. To our knowledge, this is the first report of an advanced PDAC case with sporadic dMMR, high TMB, and no Lynch Syndrome having a good response to immunotherapy.
CONCLUSIONS: This case further supports TMB and high MSI/dMMR being possible biomarkers for immunotherapy of PDAC as well as highlights the importance of both germline and somatic testing of patients with PDAC.
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