Immune checkpoint inhibitors and immune mediated diabetes mellitus: Meta-review of case reports.
Authors: Aiden Michael Van Loo, Manthan Patel, Adil Mohammed, Jun Hwan Kim, Samantha Silvers, Rami Ebrahim, Tiara Bolton, Chad Martin, Hunter Li, Zainab Muslehuddin, Rupak Desai, S. Sethu Reddy, Nicholas Haddad
Journal: Journal of Clinical Oncology (2024)

e14606 Background: Use of Immune checkpoint inhibitors (ICIs) is an increasingly popular antitumor immunotherapy targeting immunoreceptors on T lymphocytes, enhancing the anti-neoplastic immune response. ICIs are becoming first line therapy options for non-small cell lung cancer and gastric adenocarcinoma and can be used as second line for variety of others. Various endocrinologic adverse events have been reported with use of ICIs. Of these, new onset Type-1 diabetes mellitus (T1DM) is of particular interest given its significant morbidity and noted frequency of 1-5% of patients who receive ICIs. There is limited consolidated information about symptomatic presentations, risk factors, and demographics of patients developing Type 1 DM in relation to ICI use. We performed a systematic review of published case reports to identify commonalities between patient disease presentation, ICI use, and development of immune-mediated diabetes mellitus. Methods: A comprehensive systemic literature search from PubMed Web Science, CINAHL, and Google Scholars was performed identifying case reports showing development of new onset diabetes mellitus in patients using immune checkpoint inhibitors. Descriptive analysis was performed to better identify characteristics and presentation of patients. Results: Based on our parameters, 130 reports with 149 cases were included. Primary tumors among the patients comprised lung cancer (34.9%) and melanoma (31.5%). Amongst all the cases, about 88% of the patients were treated with anti-PD-1 (program cell death) receptor, with nivolumab alone (34.9%) and pembrolizumab alone (26.2%) being the most common agents. Cases were more commonly found to be males (61.7%) and of Asian (36.6%) or North American (35.6%) background. Patient ages ranged from 14-95 with a mean of 62.3. Presentation most commonly started after the third cycle (13.4%) and was noted to occur between 1-50 doses. Diabetic Ketoacidosis was diagnosed in 69.8% of individuals, and the average presenting blood glucose was 611 mg/dl with an HbA1c of 8.2%. Autoantibody data was largely missing; however, anti-GAD antibodies were noted to be present in 29.5% of cases. 34.2% of patients had coexisting endocrinopathies with thyroiditis being the most common, occurring in 20% of patients. 1.3% of patients did not survive the initial hospitalizations, with the vast majority (95.3%) remaining on insulin and a select few (2%) were eventually able to discontinue insulin. Conclusions: New onset diabetes is a rare but a potential life-threatening metabolic urgency. Thus, it is paramount that clinicians maintain close monitor of blood glucose and endocrine function when a cancer patient who recently started ICIs gets admitted for hyperglycemia. Further research is warranted to understand onset of diabetes mellitus at molecular level.