SAT-411 Vitamin D Levels and Risk of Thyroid Immune Related Adverse Events in Patients on Immune Checkpoint Inhibitors

Abstract

Immune checkpoint inhibitors (ICI), such as monoclonal antibodies to cytotoxic T lymphocyte associated protein 4 (CTLA-4), programmed cell death 1 (PD-1) and PD ligand 1 (PD-L1) are recognized as effective cancer-directed therapies. Yet, ICI-induced activation of the immune system results in immune-related adverse events (irAEs) affecting many organs, including the thyroid. Separately, Vitamin D (Vit D) deficiency has been associated with increased risk of autoimmune thyroid disease. We hypothesized that patients who were Vit D deficient at the time of initiating ICI therapy would be more likely to develop thyroid irAEs. We retrospectively collected data for 411 patients who received ICIs at our institution between January 2011 and April 2017. We then identified 91 of these patients who had 25-OH Vit D levels obtained; 2 were excluded from analysis due to previous thyroidectomy. We recorded demographics, cancer type, Vit D level closest to the start date of ICI therapy, and thyroid irAEs. Patients were categorized as Vit D deficient (<20ng/mL), insufficient (20-29.9ng/mL) or sufficient (≥30ng/mL). We compared patient demographic and clinical characteristics between the VitD categories. Proportions were compared using Fisher’s Exact Test. Of the 89 patients, 48.3% were female and 51.7% were male. Mean age was 67.2 (SD±10.6) years with 57% white, 8% black, 10% hispanic, 7% Asian, and 18% other / unknown. 20% of patients had non-small cell lung cancer, 15% melanoma, 13% hepatocellular carcinoma, 12% multiple myeloma (MM), 8% renal cell carcinoma (RCC), 7% head and neck squamous cell carcinoma, 7% urothelial carcinoma and 18% other cancer types. 21.3% were Vit D deficient, 40.4% were insufficient, and 38.2% were sufficient. Patients with Vit D deficiency and insufficiency were younger (age 64.1± 11.7, 65.9±9.5 years, respectively) than the Vit D sufficiency group (70.1±10.5years, p=0.046). No significant differences between males and females were observed between Vit D categories. Across cancer types, the highest prevalence of Vit D deficiency was in RCC (42.9%) and MM (36.4%). Hispanic and Asian patients had the highest prevalence of Vit D deficiency (44.4% and 33.3%, respectively). 11 patients (12.4%) developed a thyroid irAE. Thyroid irAEs occurred in 5.3% with Vit D deficiency, 8.1% with Vit D insufficiency, and 20% with Vit D sufficiency, but the association was not statistically significant (p=0.2). In contrast to our hypothesis, Vit D deficiency was not associated with a higher rate of thyroid irAEs. In fact our data suggest that patients who are vitamin D sufficient at the time of starting ICI therapy may be at greater risk of developing thyroid irAEs. Our study is limited by small numbers and the retrospective nature of the study. Prospective studies should be performed to determine the significance of Vit D levels on ICI related thyroid disease.