|
Title
|
|
|
|
Programmed cell death-1 inhibitor-induced type 1 diabetes mellitus
| |
|
Author
|
|
|
|
| |
|
Abstract
|
|
|
|
| Context: Pembrolizumab (Keytruda; Merck Sharp & Dohme) is a humanized IgG4 monoclonal antibody used in cancer immunotherapy. It targets the programmed cell death-1 (PD-1) receptor, which is important in maintaining self-tolerance. However, immune checkpoint blockade is associated with a risk for immune-related adverse events (irAEs) potentially affecting the endocrine organs. Type 1 diabetes mellitus is a rare irAE of PD-1 inhibitors, occurring in 0.2% of cases. Evidence Acquisition: Systematic search of four databases (MEDLINE, Embase, Web of Science, and Cochrane Library) using the search terms "diabetes" or "ketoacidosis" and "pembrolizumab," "nivolumab," "PD-1 inhibitor," or "immunotherapy." Included were articles published in English between 1 January 2012 and 1 January 2018. The search was supplemented by bibliographic searches of the complete reference lists of all included papers. Evidence Synthesis: We provide an overview of all published cases (n = 42) of PD-1 inhibitor-induced type 1 diabetes mellitus to date, including a well-characterized case of islet cell antibody and glutamic acid decarboxylase antibody-positive diabetes mellitus, in a patient with a diabetes-prone HLA genotype. She presented with diabetic ketoacidosis during pembrolizumab therapy for a metastatic uveal melanoma. Furthermore, we discuss potential pathogenic mechanisms, clinical presentation, prognostic markers (beta-cell antibodies and HLA type), treatment, and a screening protocol. Conclusions: Because the use of immunotherapy will increase, it is essential that all clinicians are aware of diabetic ketoacidosis as a rare and life-threatening side effect of immunotherapy. Blood glucose monitoring during anti-PD-1 therapy is necessary. |
| |
|
Language
|
|
|
|
English
| |
|
Source (journal)
|
|
|
|
The journal of clinical endocrinology and metabolism. - Baltimore, Md
| |
|
Publication
|
|
|
|
Washington
:
Endocrine soc
,
2018
| |
|
ISSN
|
|
|
|
0021-972X
| |
|
Volume/pages
|
|
|
|
103
:9
(2018)
, p. 3144-3154
| |
|
ISI
|
|
|
|
000444322000004
| |
|
Pubmed ID
|
|
|
|
29955867
| |
|
Full text (Publisher's DOI)
|
|
|
|
| |
|
Full text (open access)
|
|
|
|
| |
|