We find the article by Wright et al. (1) very interesting. They describe 283 cases of new-onset diabetes mellitus (DM) after treatment with checkpoint inhibitors (CPI) from the World Health Organization’s database. The aim of the study was to characterize this group of patients who developed DM after receiving treatment with CPI.
Recently, we performed a review including 25 cases with new-onset DM after treatment with CPI (2). In accordance with the findings of Wright et al. (1), we also found a wide range of time of DM onset, ranging from 7 to 365 days after receiving the first dose of CPI. In their article, Wright et al. (1) describe that 9% of case subjects developed DM more than 3 months after the last dose of CPI, which emphasizes the importance of being aware of this serious complication even after the treatment with CPI has been completed.
In addition, we agree that most of the cases of DM occur in patients treated with anti–programmed cell death protein 1 (anti-PD1) or anti–programmed death-ligand 1 (anti–PD-L1). However, the article by Wright et al. (1) is not the first to find an association between DM and monotherapy with anti–cytotoxic T-lymphocyte–associated antigen 4 (anti-CTLA4) outside of Japan. In 2017, we reported on a case of a 63-year-old woman with metastatic melanoma having new-onset DM after monotherapy with ipilimumab (anti-CTLA4) (3). The patient presented with diabetic ketoacidosis after four doses of ipilimumab. Further blood tests showed that she had a very low C-peptide level of 19 pmol/L, and she has since been treated with insulin. The HbA1c was 50 mmol/mol at referral.
As mentioned in the article by Wright et al. (1), it could have been interesting to have information on C-peptide level and autoantibodies. In the previous cases with DM after treatment with CPI, 14 out of 20 patients (5 unknown) tested positive for GAD or IA2 antibodies, which could imply an autoimmune cause of DM triggered by CPI (2). Furthermore, the C-peptide level was low or undetectable in all the published cases, and no patients regained their β-cell function (2).
We agree with the authors that many of the patients present with diabetic ketoacidosis at the time of diagnosis (50.2%) (1). In our review we found that most patients presented with ketoacidosis or severe hyperglycemia at the time of diagnosis, demonstrating a rapid development of the condition (2).
Because of the increasing use of CPI monotherapy and particularly in combination treatment, we would expect to see an increasing number of cases of DM after treatment with CPI (4). For this reason, it could be interesting to study the clinical course and the pathogenesis of DM after treatment with CPI to determine which patients are at risk for developing DM and to potentially find a treatment to regain β-cell function (5). So far, in the published cases none of the patients have regained β-cell function.
Article Information
Duality of Interest. No potential conflicts of interest relevant to this article were reported.
The authors of the cited article did not respond.
