title: Anti-PD-L1 atezolizumab-Induced Autoimmune Diabetes: a Case Report and Review of the Literature.
abstract: Programmed cell death-1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors trigger an immune-mediated anti-tumour response by promoting the activation of cytotoxic T lymphocytes. Although proven to be highly effective in the treatment of several malignancies they can induce significant immune-related adverse events (irAEs) including endocrinopathies, most commonly hypophysitis and thyroid dysfunction, and rarely autoimmune diabetes. Here we present the first case report of a patient with a primary diagnosis of urothelial cancer developing PD-L1 inhibitor-induced autoimmune diabetes. A euglycemic 57 year old male presented to clinic with dehydration after the fifth cycle of treatment with the novel PD-L1 inhibitor atezolizumab. Blood tests demonstrated rapid onset hyperglycaemia (BM 24 mmol/L), ketosis and a low C-peptide level (0.65 ng/mL) confirming the diagnosis of type 1 diabetes. He responded well to insulin therapy and was discharged with stable blood glucose levels. Due to the widening use of PD-1/PD-L1 inhibitors in cancer treatment clinicians need to be aware of this rare yet treatable irAE. Given the morbidity and mortality associated with undiagnosed autoimmune diabetes we recommend routine HbA1c and plasma glucose testing in all patients prior to and during treatment with PD-1/PD-L1 inhibitors until more evidence has accumulated on identifying those patients with a pre-treatment risk of such irAEs.
authors.affiliation: Department of Oncology, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 7LE, UK. laura.hickmott@nhs.net.
authors.forename: Laura
authors.identifier: 0000-0002-5119-6416
authors.initials: L
authors.lastname: Hickmott
authors.affiliation: Department of Oncology, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 7LE, UK.
authors.forename: Hugo
authors.initials: H
authors.lastname: De La Peña
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 7LE, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Turner
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 7LE, UK.
authors.forename: Fathelrahman
authors.initials: F
authors.lastname: Ahmed
authors.affiliation: Department of Oncology, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 7LE, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Protheroe
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 7LE, UK.
authors.forename: Ashley
authors.initials: A
authors.lastname: Grossman
authors.affiliation: Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, M20 4BX, UK.
authors.forename: Avinash
authors.initials: A
authors.lastname: Gupta
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors* / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D061026:Programmed Cell Death 1 Receptor; C000594389:atezolizumab