Immune checkpoint inhibitor-related type 1 diabetes mellitus which develops long after treatment discontinuation: a case report and review of literature

• Published in: Diabetology international 2024-07, Vol.15 (3), p.605-610
• Main Authors: Obata, Yoshinari, Takemoto, Miho, Sakaue, Taka-aki, Kawata, Satoshi, Mukai, Kosuke, Miyashita, Kazuyuki, Kozawa, Junji, Nishizawa, Hitoshi, Shimomura, Iichiro
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Autoantibodies; Case Report; Case reports; Chemotherapy; Diabetes; Diabetes mellitus (insulin dependent); Endocrinology; Glucose tolerance; Glutamate decarboxylase; Glutamic acid; Haplotypes; Histocompatibility antigen HLA; Immune checkpoint inhibitors; Immunological tolerance; Immunotherapy; Ketoacidosis; Medicine; Medicine & Public Health; Metabolic Diseases; Monoclonal antibodies
• ISSN: 2190-1678; 2190-1686
• DOI: 10.1007/s13340-024-00719-4

Immune checkpoint inhibitor (ICI)-related type 1 diabetes is an immune-related adverse event (irAE), occurring in slightly less than 1% of patients undergoing ICI therapy. Most cases develop during ICI treatment, with occurrences long after discontinuation being extremely rare. A 76-year-old woman, with no history of glucose tolerance issues, was diagnosed with lung adenocarcinoma with pleural invasion and underwent chemotherapy, including atezolizumab, an anti-programmed death-ligand 1 antibody. This treatment was discontinued due to disease progression, although she continued with other chemotherapy regimens. Approximately 5.5 months (166 days) after her last atezolizumab dose, she developed diabetic ketoacidosis, fulfilling the diagnostic criteria for fulminant type 1 diabetes. Anti-glutamic acid decarboxylase antibodies were positive. The patient carried susceptibility human leukocyte antigen (HLA) haplotypes, which are associated with type 1 diabetes. To date, including our patient, only nine cases of ICI-related type 1 diabetes developed after ICI discontinuation have been precisely reported. Eight cases originated from East Asia, with six exhibiting fulminant type 1 diabetes, and seven tested negative for islet-related autoantibodies. The reported cases were independent of ICI types, cycle number, or HLA haplotypes. Median time from the last ICI administration to diabetes onset was 4 months (range: 2–7 months). Although reports of cases occurring after ICI discontinuation are currently limited, their frequency may increase with the wider use of ICIs and improved survival rates of patients post-treatment. Therefore, it is crucial to remain vigilant for the development of ICI-related type 1 diabetes, not only during ICI administration, but also long after discontinuation.