1162 An update on immune checkpoint inhibitor-induced diabetes mellitus across NCI trials
Year: 2024
Type: conference-abstract
Abstract: Background Immune checkpoint inhibitors (CPI) are known to cause new-onset diabetes (CPI-DM). While rare, this adverse event can be challenging for clinicians and negatively impact patient quality of life. Therefore, it is important to identify risk factors and clinical characteristics of the immune related adverse event (irAE). We present an expanded comprehensive, multi-institutional study of CPI-DM across multiple agents and cancer types from clinical trials sponsored by the National Cancer Institute (NCI). Methods The NCI Cancer Therapy Program (CTEP) database of adverse events (AEs) was queried for AEs related to diabetes (grade 3 or 4 hyperglycemia, acidosis including diabetic ketoacidosis (DKA), glucose intolerance and diabetes mellitus) among all patients who had been treated with a PD-(L)1 inhibitor alone or in combination with CTLA-4 inhibitors or other agents from 6/2015 to 12/2022. Each AE report was reviewed and classified as due to CPI DM, new onset type 2 diabetes mellitus (T2DM), T2DM exacerbation without medication non-adherence, existing DM with medication non-compliance, or association with steroids (SDM). CPI-DM was diagnosed based on evidence of insulin deficiency either through presentation in DKA or low c-peptide with an ongoing insulin requirement and/or positive islet autoantibodies. Results In total, out of just over 14,400 patients treated with CPIs, there were 178 cases with at least one of these AEs; 73 (0.51%) had CPI-DM, 51 (0.35%) had SDM, 5 (0.03%) had new T2DM , 19 (0.13%) had T2DM exacerbation, 10 (0.07%) had medication non-adherence, and 20 (0.14%) had acidosis not attributable to diabetes or had insufficient data. Overall, 41% of these AEs were attributable to CPI-DM. The incidence of CPI-DM was 0.51%. Melanoma was the most frequent cancer (21/73) with an overall incidence of 1.13%. Among cancers with over 100 subjects exposed, the incidence was highest in renal cell cancer (1.41%). While PD1 inhibitor monotherapy was most frequent CPI type (40/73) among CPI-DM patients, its incidence was lower (0.38%) compared to combination CTLA-4 and PD-(L)1 inhibitors (0.96%) (chi-square p <0.01), with many patients also exposed to additional agents. Hospitalization was required for 87.5% of CPI-DM cases with 74.3% of those requiring an inpatient endocrine consult. Conclusions Among NCI CTEP sponsored trials, CPI-DM was a rare but costly irAE. CPI-DM was significantly more common in patients exposed to combination PD-(L)1 and CTLA-4 immunotherapy. Given these findings, providers in cancer types like melanoma and renal cell cancer that frequently use combination immunotherapy may need increased vigilance. Ethics Approval Consent was obtained for each trial but de-identified, human subject exempt data was used for this analysis. Consent Consent was obtained for each trial but de-identified, human subject exempt data was used for this analysis.
Authors: Zoe Quandt, Shanda Finnigan, Vanessa Hill, Joe Dib, Jason Burian, Sapir Tessler, Darah Davidson, Abdul Rafeh Naqash, Mark Anderson, Megan Othus, Elad Sharon
Institutions: University of California, San Francisco, National Institutes of Health, National Cancer Institute, University of California, Santa Barbara, University of Michigan, University of Maryland, College Park, OU Health Stephenson Cancer Center, Fred Hutch Cancer Center, Dana-Farber Cancer Institute
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,490
OpenAlex ID: W4404064818