Abstract 1186: Moving beyond conventional autoimmune thyroiditis autoantibodies to predict immune checkpoint inhibitor induced hypothyroidism
Authors: Kim Blenman, Ondrej Blaha, Courtney Gibson, Sherry Qiu, Holly Rushmeier, Milad Ibrahim, Shi Qiu, Michelle Krosgsgaard, Iman Osman
Journal: Cancer Research (2024)

Abstract INTRODUCTION: Treatment emergent adverse events (TEAEs) thyroiditis/thyrotoxicosis and hypothyroidism occur in up to 40% of patients treated with immune checkpoint inhibitors (ICIs). Conventional autoimmune thyroiditis autoantibodies (AutoAbs) (thyroglobulin (TG); thyroid peroxidase (TPO)) do not predict these TEAEs. We previously reported that pretreatment serum AutoAb profiles were associated with all severe TEAEs for melanoma patients treated with ICIs. Herein, we test if pre-existing AutoAbs could predict ICI induced hypothyroidism (TEAE ThyDis). METHODS: NYU Melanoma Program patients with stage IV metastatic melanoma treated with ICIs (Ipilumumab, Pembrolizumab, Nivolumab, or Combination) who had TEAE ThyDis (N = 14) or No TEAE (N = 11) were included. The HuProtTM human proteome microarray was used to profile proteins on cell surfaces or preferentially in extracellular spaces (N = 1061) in pretreatment and posttreatment (within ~4 months of ICI start) serum. Wilcoxon Rank Sum test was used to determine statistical significance (p &amp;lt; 0.05). RESULTS: 17 pretreatment pre-existing AutoAbs were detected (Table). All were higher in patients with TEAE ThyDis versus those with No TEAE. The pre-existing AutoAbs impacted immune cells (41%), extracellular matrix (ECM) (65%), or both (24%). P3H4 (p = 0.01) and ABCA2 (p = 0.01) were the only pre-existing AutoAbs that were statistically different posttreatment and were &amp;gt;10x higher in patients with TEAE ThyDis. They are both associated with intracellular vesicles but can be found in plasma membranes and extracellular spaces. No pre-existing AutoAbs were higher in patients with No TEAE ThyDis compared to those with TEAE ThyDis. However, posttreatment there was an increase in CSF1 AutoAbs that were not pre-existing (p = 0.05). CONCLUSIONS: Our data suggest that serum AutoAbs beyond TG and TPO can predict ICI TEAE ThyDis. Larger studies in other cancers (e.g., Breast) are required to validate these results. Pretreatment VS Posttreatment Pretreatment Pre-Existing Autoantibody Gene Name Impact TEAE ThyDis Present_median (N=14) TEAE ThyDis Absent_median (N=11) p-value COL14A1 ECM 17.35 7.99 0.01 DKK3 Cancer cells/ECM 14.74 3.75 0.01 LRFN1 Neurons 9.87 3.54 0.01 ABI3BP ECM 2.80 1.69 0.02 SELPLG Immune Cells 6.26 3.39 0.02 SMPDL3B Immune Cells/ECM 3.52 1.82 0.02 P3H4 Fibroplasts/ECM 13.41 6.29 0.02 C1QTNF2 Adipocytes/ECM 10.81 5.01 0.03 EMP1 Apoptosis 6.61 3.58 0.03 TMEF1 Neurons 6.44 3.03 0.03 CAPNS1 Cytoskeleton/ECM 3.27 2.13 0.04 FGFR2 Cancer Cells/ECM 2.96 1.62 0.04 GZMH Immune Cells 2.46 1.45 0.04 FSTL1 Immune Cells (autoantigen)/ECM 5.76 3.17 0.04 ABCA2 Immune Cells 11.81 7.00 0.05 ENPP1 Immune Cells/ECM 2.00 1.33 0.05 FGL2 Immune Cells/ECM 4.17 2.21 0.05 Posttreatment P3H4 Fibroplasts/ECM 61.82 6.09 0.01 ABCA2 Immune Cells 106.97 6.69 0.01 CSF1 Immune Cells 4.89 10.31 0.05 Citation Format: Kim Blenman, Ondrej Blaha, Courtney Gibson, Sherry Qiu, Holly Rushmeier, Milad Ibrahim, Shi Qiu, Michelle Krosgsgaard, Iman Osman. Moving beyond conventional autoimmune thyroiditis autoantibodies to predict immune checkpoint inhibitor induced hypothyroidism [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1186.