FRI539 Vitamin D and Endocrine Immune-Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitors
Authors: He Zijun , Leiter Amanda , Carroll Emily , Santiago Pichardo Gabriela , Khanna Ira , Gutowski Emily , Jane Gallagher Emily 
Published: October 2023

Disclosure: Z. He: None. A. Leiter: None. E. Carroll: None. G. Santiago Pichardo: None. I. Khanna: None. E. Gutowski: None. E.J. Gallagher: Research Investigator; Self; Novartis Pharmaceuticals, Flare Therapeutics, Seagen.

Background: Low vitamin D levels have been previously associated with the development of thyroid dysfunction in non-cancer populations. Thyroid dysfunction is one of the most common immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs). Currently, the effect of vitamin D deficiency or vitamin D supplementation on the development of ICI-induced thyroid dysfunction is unknown. This study was design to examine the association between baseline vitamin D levels and vitamin D supplementation, and the development of ICI-induced thyroid dysfunction. Methods: In this IRB-approved, retrospective cohort study, we collected demographic and clinical characteristics in addition to TSH, free T4, and vitamin D levels from patients with melanoma, multiple myeloma (MM), and transitional cell carcinoma (TCC) treated with ICIs between 2011 and 2020, in a large urban hospital system. The primary outcome was the occurrence of thyroid dysfunction defined by abnormal TSH or free T4 level after ICI initiation. Vitamin D deficiency / insufficiency was defined as serum 25-hydroxy-vitamin D level &lt;30ng/mL. Patients were followed until the first occurrence of the primary outcome or the date of the most recent normal TSH level. Descriptive data are presented as n(%) and median±SD. Univariate and multivariate analysis were performed to examine the association between the primary outcome and vitamin D deficiency/ insufficiency or supplementation. Results: 288 patients with melanoma (n=111), MM (n=86) or TCC (n=91) were identified, with a median age of 65±13 years, and 64% were male. 110 (38%) patients experienced thyroid dysfunction. Among the TCC subgroup, the mean baseline TSH levels for patients who experienced the

outcome was significantly higher than that for patients who did not (p = 0.0066). No statistical significance was found for the melanoma (p=0.42) or MM subgroups (p=0.30). Amongst patients with baseline vitamin D levels measured, we found no statistically significant association between thyroid dysfunction and baseline vitamin D deficiency (OR = 0.62, p = 0.34). In the entire cohort, the 1-year outcome-free rates for patients taking and not taking vitamin D supplementation were 68% and 61%, respectively (p=0.07). Vitamin D supplementation was found to reduce the risk of ICI-induced thyroid abnormality by approximately 40% (RR = 0.606, p=0.03) in the multivariate analysis. No difference in mortality was found between those who developed thyroid dysfunction and those who did not. Conclusions: In individuals with melanoma, MM and TCC, vitamin D supplementation may have a protective effect against ICI-induced thyroid dysfunction. Whether vitamin D supplementation impacts cancer response to ICIs is unknown at this time.

Presentation: Friday, June 16, 2023