Immune Checkpoint Inhibitor-Associated Type 1 Diabetes Mellitus: Case Series, Review of the Literature, and Optimal Management

Abstract

With the introduction of immune checkpoint inhibitors into clinical practice, various autoimmune toxicities have been described. Antibodies targeting the receptor:ligand pairing of programmed death receptor-1 (PD-1) and its cognate ligand programmed death-ligand 1 (PD-L1) in rare reports have been associated with autoimmune diabetes mellitus. We report 2 cases of rapid-onset, insulin-dependent, type 1 diabetes mellitus in the setting of administration of nivolumab, a fully human monoclonal antibody to PD-1, and atezolizumab, a humanized monoclonal antibody to PD-L1. This appears to be the first report of autoimmune diabetes mellitus associated with atezolizumab. In addition, we provide a brief review of similar cases reported in the literature and a discussion of potential mechanisms for this phenomenon and propose a diagnostic and treatment algorithm.

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.…”

Severe toxicity from checkpoint protein inhibitors: What intensive care physicians need to know?

“…Diabetes was related to pancreatic disorder or to autoimmune insulin-dependent diabetes. (Table 2) [64, 65]. Ketoacidosis may require ICU admission [64].…”

Histologically‐diagnosed psoriasiform dermatitis induced by nivolumab successfully controlled by etanercept: A case report

“…Dear Editor, Psoriasiform dermatitis induced by immune checkpoint inhibitors, one of the immune-related side effects, generally shows mild manifestations and is well-managed by topical medication and/or phototherapy. 1 This report, however, describes severe de novo psoriasiform dermatitis induced by nivolumab, a human IgG4 monoclonal antibody against programmed cell death 1 (PD-1), that improved only after using etanercept, a tumor necrosis factor-alpha (TNF-a) inhibitor.…”

“…To date, all clinical trials with anti-PD-1 have excluded patients with pre-existing autoimmune diseases. 1 In Japan, there has been a single case report of psoriatic arthritis (PsA) induced by an anti-PD-1, nivolumab. 2 Here, we report a case of PsA induced by another anti-PD-1, pembrolizumab, for advanced lung adenocarcinoma.…”