CANDIED: A Pan-Canadian Cohort of Immune Checkpoint Inhibitor-Induced Insulin-Dependent Diabetes Mellitus.
Thiago P MunizDaniel Vilarim AraújoKerry Joane SavageTina ChengMoumita SahaXinni SongSabrina GillJose G MonzonDebjani GrenierSofia GentaMichael J AllenDiana Paola Arteaga CeballosSamuel D SaibilMarcus O ButlerAnna SpreaficoDavid HoggPublished in: Cancers (2021)
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.
Keyphrases
- end stage renal disease
- ejection fraction
- chronic kidney disease
- newly diagnosed
- type diabetes
- prognostic factors
- peritoneal dialysis
- stem cells
- mesenchymal stem cells
- adipose tissue
- clinical trial
- randomized controlled trial
- skeletal muscle
- high glucose
- diabetic rats
- open label
- squamous cell
- replacement therapy
- basal cell carcinoma