Clinical characterization and association with autoimmunity in immune checkpoint inhibitor (ICI)–mediated thyroid dysfunction in a real-world sample.

Abstract

e24159 Background: ICI mediated thyroid dysfunction (TD) usually presents as transient hyperthyroidism followed by hypothyroidism or as isolated hypothyroidism. Antibodies (Abs) associated with autoimmune TD (Hashimoto’s and Grave’s disease) include antibodies against thyroid peroxidase (TPO), thyroglobulin (TgAb), and thyroid stimulating immunoglobulin (TSI). Current guidelines do not have recommendations for monitoring these Abs during ICI therapy. We studied a racially diverse, real-world sample of patients (pts) treated with ICI who developed TD to better characterize the role of auto-Abs in these toxicities. Methods: This is a retrospective study utilizing a real-world clinical dataset of 1927 pts treated with ICI within the MedStar-Georgetown health system. A cohort of pts with immune mediated TD were extracted from the GU Immunotherapy registry and included in this analysis. Results: 173 pts experienced ICI-related TD: 84 (48.6%) female, 37 (21.4%) African American, 121 (70.0%) White, average age 63.7 (22-94). 59 (34.1%) experienced a hyperthyroid (hyperTD) phase followed by hypothyroidism (hypoTD), 15 (8.7%) experienced a hyperTD that resolved without permanent hypoTD, and 99 (57.2%) experienced hypoTD without an associated hyperTD. Frequency of testing and presence of anti-thyroid Abs were TPO (20/27, 74.1%), TSI (5/14, 35.7%), and TgAb (6/13, 46.2%). Overall, TPO Ab positivity was found to be higher than TgAb in this study (74.1% vs 46.2, p=0.0829). The average time from initiation of ICI to development of hyperTD was 54.9 days (9-242), and average time from onset of hyperTD to development of hypoTD was 57.1 days (4-287). Higher response rates were seen in pts who tested positive for TPO (13/20, 65% vs 2/7, 29%, p=0.095). Out of 1213 pts with available autoimmune history, 102/1213 (8.4%) had a history of hypoTD, 13/173 (7.5%) with TD had a known history. Pts with a TD history had a numerically higher rate of TD however not statistically significant (13.7% vs 10.2%, p=0.2618). Those experiencing thyroid toxicity were more likely to respond to immunotherapy (68.5% vs 39.2%, p=0.001). Conclusions: Presence of thyroid autoAbs in cases of ICI-TD suggests an autoimmune etiology. The high rates of Abs suggests that pre-existing subclinical autoimmunity becomes unleashed after the administration of ICI. Given the known correlation between ICI-related endocrine toxicity and ICI response, future studies of thyroid Ab presence could be used to identify populations with higher rates of both ICI TD toxicity and treatment response. TPO TSI TgAb Lung 63 8/11 (72.7%) 3/5 (60%) 2/2 (100%) Melanoma 52 7/8 (87.5%) 1/4 (25%) 3/5 (60%) Total 173 20/27 (74.1%)0-6683 5/14 (35.7%)0-99 6/13 (46.2%)0-555