Atezolizumab induced new-onset type 1 diabetes mellitus

J Oncol Pharm Pract. 2023 Jul;29(5):1268-1270. doi: 10.1177/10781552231151656. Epub 2023 Jan 12.

Abstract

Introduction: Immune checkpoint inhibitors (ICI) are novel therapeutic strategies in cancer treatment, promoting anti-tumor response by boosting cytotoxic T lymphocytes. Despite their high effectiveness, they can trigger the activation of diverse autoimmune diseases in genetically predisposed individuals. New-onset autoimmune diabetes mellitus type 1 (T1D) is an extremely unusual side effect, described in less than 1% of patients.

Case report: Here we present a 44-year-old male diagnosed with non-surgical hepatocarcinoma, developing programmed death ligand-1 inhibitor-induced autoimmune endocrinopathies, presented as diabetic ketoacidosis and thyroiditis. After two cycles of atezolizumab and bevacizumab, he consulted the emergency department with abdominal pain and diabetes cardinal features (polyuria, polydipsia, vomiting). Blood tests demonstrated hyperglycemia >800 mg/dL, capillary ketonemia >3 mmol/L, metabolic acidosis (pH 7.24 with HCO3 14 mEq/L). Subsequent studies detected a low level of C-peptide, and positive glutamic acid decarboxylase and insulinoma-associated antigen-2 antibodies. Thyroid examination was compatible with thyroiditis, showing a high free thyroxine level (1.91 ng/dL) with low thyrotropin (TSH) (0.08 mIU/L) and negative anti-TSH receptor antibody.

Management & outcome: After reaching metabolic stabilization, treatment with Atezolizumab was restarted, with no further complications showing size stability in the computed tomography control.

Discussion: T1D related to ICI is a rare condition that presents as a life-threatening emergency and should be recognized and treated early. Blood glucose and glycated hemoglobin determinations should be performed at periodic visits for detection. There are genetic factors that predispose susceptible individuals, but there is no evidence of studies to be performed before the onset of ICI or preventive strategies.

Keywords: Atezolizumab; anti-PD-L1; immune-checkpoints inhibitors; thyroiditis; type 1 diabetes mellitus.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antineoplastic Agents* / adverse effects
  • Diabetes Mellitus, Type 1* / chemically induced
  • Diabetes Mellitus, Type 1* / drug therapy
  • Humans
  • Male
  • Thyroiditis* / chemically induced

Substances

  • atezolizumab
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents