447P - Clinical characteristics of 21 patients with type 1 diabetes mellitus related to immune checkpoint inhibitors

Background

Immune checkpoint inhibitor (ICI)-associated type 1 diabetes mellitus (T1DM) is a rare, but potentially life-threatening adverse event. However, clinical picture of this irAE remains largely unknown due to its low incidence. The aim of this study was to identify the characteristics and clinical course of ICI-associated T1DM for early detection and treatment.

Methods

We retrospectively reviewed 21 patients (pts) who developed T1DM during treatment with ICIs from October 2015 to March 2021 at the multicenter. The pts’clinical characteristics and laboratory and radiologic findings were collected.

Results

The characteristics were as follows: median age, 63 years (range, 32-75); male/female, 16/5; PS 0/1/3, 10/10/1; treatment Nivolumab/Nivolumab plus Ipilimumab, 14/7. The median time of clinical diagnosis was 3.3 months (range, 0.8-30.8), and the median number of ICI administrations before onset was 7 times (range, 1-57). Symptoms at the onset of T1DM included hyperglycemic symptoms (thirst, polydipsia, polyuria) in 14 pts (66.7%), abdominal symptoms in 11 pts (52.4%), flu-like symptoms in 6 pts (28.6%). The mean ± standard deviation or median glucose levels, HbA1c levels and serum C-peptide immunoreactivity levels at diagnosis were 556±336 mg/dL, 7.7±1.4 % and 0.40 ng/mL (range, 0.03-5.50), respectively. Diabetic ketoacidosis (DKA) was described in 9 pts (42.9%) and their median arterial pH was 7.190 (range, 7.019-7.373). Anti-glutamic acid decarboxylase antibodies were tested in 20 pts and were positive in 3 pts (15.0%). Of the 22 pts, 7 pts (33.3%) met the criteria of fulminant T1DM.

Conclusions

Patients with T1DM induced by ICIs showed similar symptoms to those of general T1DM, but those were not always present in each case. Of note, in about 60% of the cases the diagnosis of T1DM was made before the development of overt DKA. In some cases, moderate hyperglycemia found incidentally at the scheduled visit led to the diagnosis of T1DM. Therefore, routine measurement of plasma glucose levels should be mandatory for early detection of ICI-associated T1DM and if suspected, prompt initiation of insulin treatment should be considered to avoid life-threatening metabolic alterations.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Japanese Society of Pharmaceutical Oncology.

Disclosure

All authors have declared no conflicts of interest.