Objective: The significance of thyroid peroxidase (TPOAb) and thyroglobulin antibody (TgAb) in the pathogenesis of thyroid immune related adverse events (irAEs) and their relationship to cancer survival outcomes are unknown. We studied TPOAb and/or TgAb positivity in thyroid irAEs related to immune checkpoint inhibitor (ICI) treatment.
Design: Retrospective cohort study conducted through Australian academic teaching hospitals.
Patients: Patients with advanced or metastatic melanoma receiving immune checkpoint inhibitor treatment.
Measurements: TPOAb, TgAb and interleukin-6 (IL-6) were measured at baseline and repeated at diagnosis in thyroid irAE patients or 30-60 days after start of ICI-treatment in euthyroid patients.
Results: 122 patients received ICI-treatment. Baseline elevation of TPOAb or TgAb was present in 19 (16%) and 28 (23%) patients, respectively. Patients with overt thyrotoxicosis (n=37) were more likely to have an elevated TPOAb and/or TgAb at baseline and had a higher median TPOAb and TgAb titre compared to patients with subclinical thyrotoxicosis (n=47) or persistent euthyroidism (n=31). Overt thyrotoxicosis was associated with significant increases in TPOAb and TgAb during treatment, which was not observed in patients who remained euthyroid or patients with other thyroid irAE subtypes. Positive TPOAb at baseline was associated with improved PFS in all patients (HR 0.30, 95% CI 0.09-0.99, p=0.04), driven mainly by patients with overt thyrotoxicosis (HR 0.08, 95% CI 0.01-0.79, p=0.03). Baseline IL-6 levels were not associated with thyroid irAE onset but did significantly increase during treatment in patients who developed overt hypothyroidism.
Conclusions: TPOAb positivity at baseline was more prevalent in patients with overt thyrotoxicosis and was associated with improvements in PFS. TPOAb positivity may be a useful biomarker to identify patients at risk of overt thyrotoxicosis irAEs and patients with increased likelihood of response to ICI-treatment.