Anti-PD-L1 atezolizumab-Induced Autoimmune Diabetes: a Case Report and Review of the Literature

Abstract

Programmed cell death-1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors trigger an immune-mediated anti-tumour response by promoting the activation of cytotoxic T lymphocytes. Although proven to be highly effective in the treatment of several malignancies they can induce significant immune-related adverse events (irAEs) including endocrinopathies, most commonly hypophysitis and thyroid dysfunction, and rarely autoimmune diabetes. Here we present the first case report of a patient with a primary diagnosis of urothelial cancer developing PD-L1 inhibitor-induced autoimmune diabetes. A euglycemic 57 year old male presented to clinic with dehydration after the fifth cycle of treatment with the novel PD-L1 inhibitor atezolizumab. Blood tests demonstrated rapid onset hyperglycaemia (BM 24 mmol/L), ketosis and a low C-peptide level (0.65 ng/mL) confirming the diagnosis of type 1 diabetes. He responded well to insulin therapy and was discharged with stable blood glucose levels. Due to the widening use of PD-1/PD-L1 inhibitors in cancer treatment clinicians need to be aware of this rare yet treatable irAE. Given the morbidity and mortality associated with undiagnosed autoimmune diabetes we recommend routine HbA1c and plasma glucose testing in all patients prior to and during treatment with PD-1/PD-L1 inhibitors until more evidence has accumulated on identifying those patients with a pre-treatment risk of such irAEs.

The spectrum, incidence, kinetics and management of endocrinopathies with immune checkpoint inhibitors for metastatic melanoma

“…Anti-PD-L1 agents were not assessed in this study; however, they may have behaved differently to anti-PD-1 therapies (17). Anti-PD-L1 is associated with the development of autoimmune diabetes; however, the spectrum of endocrinopathies with these therapies require further study (18). In contrast to our study, other groups have reported ipilimumab monotherapy to result in a lower rate of endocrine immune adverse events relative to combination dual-therapy (3,10).…”

Case of fulminant type 1 diabetes induced by the anti‐programmed death‐ligand 1 antibody, avelumab

“…To the best of our knowledge, this is the first report of a patient with fulminant type 1 diabetes mellitus induced by ICI monotherapy with avelumab. A case with fulminant type 1 diabetes mellitus due to anti‐PD‐L1 antibody, atezolizumab, and cases with type 1 diabetes due to anti‐PD‐L1 antibody, atezolizumab or durvalumab, have been reported. The patients with fulminant type 1 diabetes mellitus due to atezolizumab developed diabetic ketoacidosis.…”

Diabetes and Blood Glucose Disorders Under Anti-PD1

“…More than cases of type 1 acute diabetes, most of them diagnosed in patients treated for a melanoma, have been reported so far in the literature, under anti-PD1, 1 under anti-CTLA4 and anti-PD1 combination and 3 under anti-PDL1 [7][8][9]11,[17][18][19][20][21][24][25][26][27][28][29][30]. (Table 4).…”

“…While no warning signal for diabetes induced by checkpoint inhibitors has been detected during the clinical trials, several cases of acute insulin-dependent type 1 diabetes (AD1) have been recently reported under anti-PD1, and anti-PDL1 antibodies [8][9][10], and more recently under the anti-CTLA4 and anti-PD1 combination [11].…”