Delayed-onset Fulminant type 1 Diabetes Mellitus after the Discontinuation of Pembrolizumab Immunotherapy: A Case Report

Abstract Introduction:Immune checkpoint inhibitors (ICI) have become an essential component of several cancer therapies, but the increasing use of such drugs has led to an increasing number of reports on immune-related adverse events (IRAEs). Although type 1 diabetes mellitus (T1DM) and its subtype, fulminant T1DM, have been reported as potential IRAEs, the development of these diseases with a delayed onset after the cessation of ICI administration is uncommon. We present the first case of delayed-onset fulminant T1DM precipitated by pembrolizumab, an ICI.Case Presentation:A 75-year-old Japanese man, who received 10 cycles of pembrolizumab as adjuvant chemotherapy for urothelial carcinoma, presented in our emergency department with polyuria and worsening dyspnea nine weeks after the discontinuation of pembrolizumab. The laboratory data showed hyperglycemia (1349 mg/dL), metabolic acidosis, HbA1c 8.1%, and serum β-hydroxybutyrate 13.9 mmol/L. The patient was diagnosed with diabetic ketoacidosis (DKA). His symptoms improved by intravenous hydration and an insulin drip. Additional workup showed his absence of insulin-secreting capacity and negative for anti-glutamic acid decarboxylase antibody.Conclusions:Fulminant T1DM as an IRAE is an oncologic emergency characterized by abrupt-onset ketoacidosis with severe hyperglycemia. In addition to the potential onset of fulminant T1DM during the course of pembrolizumab treatment, clinicians should consider the possibility of delayed-onset fulminant T1DM with DKA, even after the discontinuation of pembrolizumab.