CANDIED: A Pan-Canadian Cohort of Immune Checkpoint Inhibitor-Induced Insulin-Dependent Diabetes Mellitus

SIMPLE SUMMARY: Immune checkpoint inhibitor-induced insulin-dependent diabetes mellitus (ICI-induced IDDM) is an emerging form of autoimmune diabetes. We describe the characteristics of 34 patients who developed ICI-induced IDDM across five Canadian cancer centres. We observed that presentation with hyperglycemic crisis is common and that patients treated with combination immunotherapy regimens develop ICI-induced IDDM earlier than those treated with monotherapy. Our results suggest that ICI-induced IDDM is irreversible but is associated with high tumor response rates and prolonged survival. The data generated by this study may help clinicians manage ICI-induced IDDM. ABSTRACT: Immune checkpoint inhibitor (ICI)-induced insulin-dependent diabetes mellitus (IDDM) is a rare but potentially fatal immune-related adverse event (irAE). In this multicentre retrospective cohort study, we describe the characteristics of ICI-induced IDDM in patients treated across five Canadian cancer centres, as well as their tumor response rates and survival. In 34 patients identified, 25 (74%) were male and 19 (56%) had melanoma. All patients received anti-programed death 1 (anti-PD1) or anti-programmed death ligand-1 (anti-PD-L1)-based therapy. From ICI initiation, median time to onset of IDDM was 2.4 months (95% CI 1.1–3.6). Patients treated with anti-PD1/PD-L1 in combination with an anti-cytotoxic T lymphocyte antigen 4 antibody developed IDDM earlier compared with patients on monotherapy (1.4 vs. 3.9 months, p = 0.05). Diabetic ketoacidosis occurred in 21 (62%) patients. Amongst 30 patients evaluable for response, 10 (33%) had a complete response and another 10 (33%) had a partial response. Median overall survival was not reached (95% CI NE; median follow-up 31.7 months). All patients remained insulin-dependent at the end of follow-up. We observed that ICI-induced IDDM is an irreversible irAE and may be associated with a high response rate and prolonged survival.