A case of fulminant Type 1 diabetes following anti-PD1 immunotherapy in a genetically susceptible patient

Immunotherapy. 2017 Jun;9(7):531-535. doi: 10.2217/imt-2017-0020.

Abstract

Programmed cell death-1 protein (PD-1) is an immune checkpoint that has gained popularity in the treatment of several advanced cancers. Inhibiting this checkpoint is known to enhance immune response, but is also known to diminish immune tolerance and to increase autoimmune toxicity. We discuss a case of rapid onset fulminant Type 1 diabetes induced by treatment with anti-programmed cell death-1 monoclonal antibody, nivolumab, in a patient with late-stage non-small-cell lung adenocarcinoma. The patient had no history of previous diabetes but did reveal a high-risk genotype for Type 1 diabetes development (DR3-DQ2; DR4-DQ8). This finding supports that acute Type 1 diabetes can be an important adverse effect of immunotherapies targeting T-cell activation regulation. Because of the severity of this adverse effect, physicians should be aware of it, and studies directed to the detection of new biomarkers for early risk stratification (e.g., HLA) should be sought.

Publication types

  • Case Reports

MeSH terms

  • Adenocarcinoma / complications
  • Adenocarcinoma / diagnosis*
  • Adenocarcinoma / drug therapy
  • Aged
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Diabetes Mellitus, Type 1 / diagnosis*
  • Diabetes Mellitus, Type 1 / etiology
  • Diabetes Mellitus, Type 1 / genetics
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • HLA-DQ Antigens / genetics
  • HLA-DR3 Antigen / genetics
  • HLA-DR4 Antigen / genetics
  • Humans
  • Immunotherapy / adverse effects
  • Immunotherapy / methods*
  • Lung Neoplasms / complications
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / drug therapy
  • Nivolumab
  • Programmed Cell Death 1 Receptor / immunology
  • Risk

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • HLA-DQ Antigens
  • HLA-DQ2 antigen
  • HLA-DQ8 antigen
  • HLA-DR3 Antigen
  • HLA-DR4 Antigen
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Nivolumab