Durable response after immune checkpoint inhibitor-related diabetes in mismatch repair deficient pancreatic cancer

Mismatch repair protein deficiency occurs in 0.8-2% of pancreatic ductal adenocarcinomas and confers susceptibility to immunotherapy. Herein, we report the case of a patient with Lynch syndrome-associated, locally advanced mismatch repair protein deficiency pancreatic ductal adenocarcinomas who demonstrated a sustained response to second-line treatment with pembrolizumab, but eventually developed immune-related diabetic ketoacidosis requiring discontinuation of treatment. He has since remained in remission, off treatment, over the following 3 years, with regular surveillance showing no clinical or radiographic evidence of disease progression. The patient's unusual disease course raises the question of whether this serious immune-related adverse event affecting the organ of malignant involvement may have predicted his remarkable and durable response. Lay abstract A small subgroup of pancreatic cancers have mutations preventing effective repair of damaged DNA; a condition termed 'mismatch repair protein deficiency'. These tumors are often effectively treated with immunotherapy. Here we describe a patient whose mismatch repair protein deficiency pancreatic cancer responded well to pembrolizumab immunotherapy, but who later developed diabetes as an immunotherapy-related adverse effect. Treatment was stopped, but his tumor remained stable off treatment over the next 3 years. His unique clinical course raises the question of whether the development of diabetes, a pancreas-specific adverse effect, may have predicted the effective treatment of pancreatic cancer.