Nivolumab-induced autoimmune diabetes mellitus presenting as diabetic ketoacidosis in a patient with metastatic mucosal melanoma

• Published in: Journal of oncology pharmacy practice Vol. 29; no. 5; p. 1259
• Main Authors: Goff, Catherine B, Plaxe, Steven C, White, Wendy, Dasanu, Constantin A
• Format: Journal Article
• Language: English
• Published: England 01.07.2023
• Subjects: Aged; Blood Glucose; Blood Glucose Self-Monitoring - adverse effects; Diabetes Mellitus, Type 1 - chemically induced; Diabetes Mellitus, Type 1 - diagnosis; Diabetic Ketoacidosis - chemically induced; Diabetic Ketoacidosis - complications; Diabetic Ketoacidosis - diagnosis; Glutamate Decarboxylase - adverse effects; Humans; Immune Checkpoint Inhibitors - adverse effects; Insulins - adverse effects; Male; Melanoma - complications; Nivolumab; mucosal melanoma; autoimmune diabetes; diabetic ketoacidosis; Nivolumab; human leukocyte antigen haplotypes
• ISSN: 1477-092X
• DOI: 10.1177/10781552221148973

Nivolumab is an immune checkpoint inhibitor used in the treatment of several malignancies. A number of immune-related endocrinopathies have been linked to its use. We report a unique case of a 74-year-old man with well-controlled diabetes mellitus type 2 and metastatic mucosal anorectal melanoma who presented with diabetic ketoacidosis after receiving his third cycle of nivolumab 240 mg intravenous (IV) every 2 weeks. He was found to have autoantibodies against glutamic acid decarboxylase 65. Genotyping for human leukocyte antigens showed the presence of DQB1*02:01 and DRB1*03:01. His presentation was complicated by acute renal failure. He required aggressive fluid resuscitation and insulin supplementation to reverse severe acid-base disturbance and multiple electrolyte abnormalities. After an 8-week interruption, the patient restarted nivolumab without any further evidence of adverse events over the next 12 weeks. He continues to require insulin replacement therapy. Development of type 1 diabetes with the use of immune checkpoint inhibitors has been increasingly reported in the literature. The exact mechanism for autoimmune diabetes precipitated by nivolumab is yet to be elucidated. Patient education about the symptoms of diabetes and regular glucose monitoring cannot be overemphasized. Testing for antibodies against glutamic acid decarboxylase 65, insulin receptors, and islet cells may also prove useful. Human leukocyte antigen DQ and DR haplotyping prior to immune checkpoint inhibitor treatment might help determine susceptibility toward developing type 1 diabetes, and provide opportunities for earlier recognition, intervention, and possibly prevention.