Anti-PD-L1 therapy and the onset of diabetes mellitus with positive pancreatic autoantibodies

BMJ Case Rep. 2017 Oct 4:2017:bcr2017220415. doi: 10.1136/bcr-2017-220415.

Abstract

An 84-year-old woman with metastatic squamous cell carcinoma of the nasopharynx and no history of diabetes was started on the antiprogrammed cell death ligand-1 (anti-PD-L1) antibody durvalumab. Four months later, she presented in diabetic ketoacidosis with glucose 488 mg/dL, anion gap 16, positive serum ketones and A1C9.1%. Antiglutamic acid decarboxylase 65 (GAD) antibody was 13 U/mL (normal, <0.5 U/mL), c-peptide 0.4 ng/dL (normal, 1.1-4.3 ng/mL) and glucose 142 mg/dL. A man with metastatic papillary urothelial carcinoma was treated with the PD-L1 inhibitor atezolizumab. He had no history of diabetes. Nine weeks after initiation, he developed fatigue and polyuria with blood glucose 336 mg/dL, c-peptide 0.6 ng/mL, A1C8.2% and GAD antibodies 28.4 U/mL (normal, <1 U/mL). Due to the diagnosis of autoimmune diabetes, both patients were treated with insulin. Autoimmune diabetes is a rare immune-related adverse effect of PD-L1 inhibitors. We present the first two cases with documented positive pancreatic autoantibodies.

Keywords: chemotherapy; contraindications and precautions; diabetes.

Publication types

  • Case Reports

MeSH terms

  • Aged, 80 and over
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / adverse effects*
  • Autoantibodies / blood
  • Carcinoma, Papillary / drug therapy
  • Carcinoma, Squamous Cell / drug therapy
  • Diabetes Mellitus, Type 1 / chemically induced
  • Diabetes Mellitus, Type 1 / diagnosis*
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetic Ketoacidosis / chemically induced
  • Diabetic Ketoacidosis / diagnosis*
  • Diabetic Ketoacidosis / immunology
  • Female
  • Humans
  • Male
  • Nasopharyngeal Neoplasms / drug therapy
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Urethral Neoplasms / drug therapy

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Autoantibodies
  • Programmed Cell Death 1 Receptor
  • durvalumab
  • atezolizumab