Pan-Canadian cohort of immune checkpoint inhibitor-induced insulin-dependent diabetes mellitus (CANDIED).

Abstract

2640 Background: Endocrine immune-related adverse events (irAEs) are frequent with immune checkpoint inhibitors (ICIs); however, ICI-related insulin-dependent diabetes mellitus (IDDM) is a rare but serious endocrine irAE. We describe the characteristics of patients who developed ICI-related IDDM across five academic Canadian cancer centres. Methods: In this multicentre, retrospective study, we included both patients who developed IDDM and patients with non-IDDM (NIDDM) or pre-DM who became insulin-dependent while on treatment with ICI. We collected data on primary tumor type, ICI regimen (single agent or combination), time to development of IDDM from ICI initiation, comorbidities, laboratory parameters at the time of IDDM diagnosis, tumor response and survival. A p value < 0.05 was considered statistically significant. Results: We identified 27 patients between July 2016 and August 2019. Median age was 60 (39-79) years, 20 (74%) were male, 15 (55%) had melanoma and 4 each (15%) non-small cell lung cancer (NSCLC) and renal cell carcinoma. Seven (26%) patients had prior NIDDM or pre-DM; 5 (18%) had an auto-immune disease (2 psoriasis, 2 inflammatory bowel disease, and 1 systemic lupus erythematosus). Laboratory parameters at presentation and management of IDDM are presented in the Table. Mean A1c was not statistically different between patients with or without prior NIDDM or pre-DM (8.4% vs. 8.6%; p = 0.9). All IDDM events were irreversible; 1 (4%) patient died of diabetic ketoacidosis. At time of IDDM diagnosis, 17 (63%) patients were receiving single agent anti-PD1 and 10 (37%) anti-PD1-based combinations (7 anti-CTLA-4, and 3 other compounds). Median time for development of IDDM from ICI initiation was 2.7 months (95% CI 0.2-5.3). Patients receiving combination ICI developed IDDM earlier than those treated with single agent (1.4 vs 4.8 months; p = 0.05). Amongst patients with metastatic disease (n = 24), 9 (38%) had a complete response and 7 (29%) had a partial response. Two patients (8%) were treated in the adjuvant setting; 1 (4%) received consolidation ICI. IDDM led to ICI discontinuation in 12 (44%) patients. After a median follow up of 21 months from ICI initiation, median survival was 30 months (95% CI NE) and was not reached in patients with melanoma and NSCLC. Conclusions: ICI-related IDDM is a rare and typically irreversible irAE that occurs early in the course of treatment and develops earlier with combination ICI. In this cohort, patients who developed ICI-related IDDM had a high tumor response rate and prolonged survival, especially melanoma and NSCLC patients. Prospective evaluation of autoantibodies to predict development of IDDM is ongoing.[Table: see text]