A Case of Pancreatic Cancer with High Tumor Mutation Burden Showing a Remarkable Response to Pembrolizumab

INTRODUCTION: Pancreatic cancer (PC) is an aggressive malignancy with limited therapeutic options and generally poor responsiveness to immune checkpoint inhibitors (ICIs). Microsatellite instability-high (MSI-High) and tumor mutation burden-high (TMB-High) phenotypes are rare, each occurring in approximately 1% of PC cases, but may predict improved response to ICIs. We report a case of recurrent PC harboring both MSI-High and markedly elevated TMB, in which pembrolizumab achieved an exceptional and durable response. CASE PRESENTATION: . Pembrolizumab was initiated, leading to rapid normalization of CA19-9 and continuous tumor shrinkage. The best overall response was classified as PR, and this PR has been maintained. At 26 months after surgery, the patient remains on pembrolizumab with sustained clinical benefit and no significant immune-related adverse events. CONCLUSIONS: This case highlights the potential for exceptional and durable response to pembrolizumab in PC characterized by concurrent MSI-High and markedly elevated TMB. Given the rarity of these biomarkers and the typically poor prognosis of PCs, early genomic profiling may facilitate personalized treatment strategies and improve outcomes in selected patients.