A Case of Nivolumab-Induced Acute-Onset Type 1 Diabetes Mellitus in Melanoma

Abstract

Nivolumab, an anti–PD-1 antibody, is now considered an important therapeutic agent in several advanced malignancies. However, immune-related adverse events such as endocrinopathies have been reported with its use. Thyroid disorder and isolated adrenocorticotropic hormone deficiency have frequently been reported as nivolumab-induced immune-related adverse events. Another endocrinopathy is nivolumab-induced type 1 diabetes mellitus (t1dm), described as diabetes mellitus with rapid onset and complete insulin insufficiency, at times leading to fulminant t1dm. We report the case of a 68-year-old woman who developed pancreatic islet–related autoantibody-negative t1dm, possibly induced by nivolumab, under continuous glucocorticoid administration. She was treated with nivolumab for advanced malignant melanoma, concomitant with 10 mg prednisolone daily for thrombophlebitis tapered to 5 mg after 13 courses of nivolumab therapy. At approximately the 27th course of nivolumab therapy, she showed elevated plasma glucose levels despite preserved insulin secretion. A month later, she developed diabetic ketoacidosis. Her insulin secretion decreased and finally was exhausted. She was diagnosed with acute-onset rather than fulminant t1dm because of a rapidly progressive course to diabetic ketoacidosis during just more than 1 week. She is currently receiving insulin replacement. There has been no recurrence of the melanoma. Thus, nivolumab might induce autoimmune diabetes mellitus, with patients having t1dm-sensitive human leucocyte antigen being more susceptible even when receiving glucocorticoids. Physicians should be aware that nivolumab could potentially induce t1dm as a critical immune-related adverse event..

Unravelling Checkpoint Inhibitor Associated Autoimmune Diabetes: From Bench to Bedside

“…This patient's C-peptide levels were never overtly low and this case is confounded by steroid use (113). Use of corticosteroids with the intent to halt CIADM or other concurrent irAE is not effective (114)(115)(116)(117). Overall, there is no current evidence to support use of immune suppression in CIADM.…”

Fulminant type 1 diabetes: A comprehensive review of an autoimmune condition

“…The correlation of FT1D and DIHS remains elusive. In addition, an increasing number of cases of FT1D that develop after the administration of immune CPIs such as anti‐programmed cell death protein 1 (PD‐1) agent nivolumab, 18,47‐51 pembrolizumab, 52‐55 and anti‐cytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4) agent ipilimumab 56 during immunotherapy for metastatic cancer. These CPI‐induced FT1D cases were reported as immune‐related adverse events.…”

Fulminant type 1 diabetes: recent research progress and future prospects

“…The HLA phenotype was determined in several case reports whereupon HLA-DR9 (an allele conferring susceptibility to type 1 diabetes) was frequently observed in the patients with type 1 diabetes related to anti-PD-1/PD-L1 therapy (Table 1) [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37].…”