Thyroid dysfunction and immune checkpoint inhibitor outcomes.

Abstract

e15103 Background: Immune checkpoint inhibitors (ICI) frequently cause thyroid dysfunction. We performed a longitudinal analysis of thyroid function tests in a large, single-center cohort of patients with multiple cancer types receiving ICI. Methods: We performed a retrospective medical records review of consecutive patients treated with ICI from 1/1/2005 to 12/31/2018. We collected demographic and clinical data, including serial thyroid function tests. We compared overall survival between patients with normal and abnormal thyroid stimulating hormone (TSH) at baseline and after ICI initiation using Kaplan-Meier curves, log-rank tests, and multivariate Cox proportional hazards model. Results: A total of 910 patients were included: 63% male, 82% white, median age 67. The most common cancer types were lung (26%), kidney (18%), and melanoma (17%). ICI types were anti-PD1/L1 (78%), anti-CTLA-4 (7%), and combination ICI (15%). Normal baseline TSH and abnormal post-treatment TSH was associated with longer overall survival (median survival 26 months) compared to all other TSH permutations (median survival < 10 months) ( P< 0.001). This finding persisted after multivariate Cox regression adjustment for age, gender and cancer type (P < 0. 001), and also after sensitivity analysis censoring patients who died within 2 months after starting ICI. Conversely, abnormal TSH at baseline was associated with lower overall survival (median 8 months) compared to normal TSH at baseline (median 18 months) ( P< 0.001), which also persisted in multivariate analysis ( P< 0.001). Kidney and head and neck cancers (71% and 69%) were associated with increased development of thyroid dysfunction compared to melanoma, lung and other urological cancers (52%, 50% and 35%) ( P< 0.01). Conclusions: Although abnormal thyroid function after ICI initiation was associated with improved overall survival, pre-treatment thyroid abnormalities were associated with worse overall survival. Given the prevalence of thyroid abnormalities in the general population, further research into these observations is warranted.