Serologic predictors of thyroid immune-related adverse events during immune checkpoint inhibitors therapy: a retrospective cohort study

Rationale: Immune-related adverse events (irAEs) are a specific type of drug toxicity that can occur in cancer patients undergoing immunotherapy with immune checkpoint inhibitors (ICIs). Endocrine irAEs rank the 3rd after the skin and gastrointestinal ones. Clinical course of endocrine irAEs usually results in irreversible damage of the glands function. Prevailing thyroid disorders among endocrine irAEs, their reactivity compared to that of autoimmune thyroiditis, the risk of potential temporary or complete withdrawal of the immunotherapy would make it necessary to search for markers able to identify the most susceptible patient groups. Aim: To evaluate an association between baseline laboratory parameters (hormonal, biochemical, and serological) in patients with malignant solid neoplasms before the first course of anti-tumor immunotherapy with ICIs in monotherapy and the subsequent development of thyroid irAEs. Methods: In this retrospective cohort we analyzed medical files from 102 adult patients (50 (49%) men, median age 60 years) with confirmed solid malignant tumors who were treated in two specialized in-patient departments from January 2020 to February 2022. Their baseline blood samples for subsequent evaluation of thyroid function, carbohydrate and calcium metabolism, as well as to exclude adrenal insufficiency were taken before the initiation of the first course of specific immunotherapy with ICIs. Thereafter, the patients were monitored for any registered irAE for up to 34 months from the beginning of the antitumor immunotherapy with ICIs. Results: Thyroid irAEs were registered in 13/102 (12.7%) patients. Only two markers were significantly associated with the development of thyroid disorders under immunotherapy with ICIs: baseline levels of anti-thyroperoxidase antibodies (TPOAb) ≥ 7.54 IU/mL (reference range (RR) 0–5.6) and anti-thyroglobulin antibodies (TgAb) ≥ 16.45 IU/mL (RR 0–115) (p 0.001). For TPOAb ≥ 7.54 IU/mL and TgAb ≥ 16.45 IU/mL, the areas under the ROC curve (AUC) were 0.828 [95% confidence interval (CI) 0.678–0.979] and 0.875 [95% CI 0.742–1.000], diagnostic sensitivity was 75% [95% CI 48–92] and 92% [95% CI 64–100], diagnostic specificity 92% [95% CI 85–96] and 84% [95% CI 77–86], prognostic values of the positive result 69% [95% CI 44–85] and 58% [95% CI 40–63], and prognostic values of the negative results 94% [95% CI 87–98] and 98% [95% CI 90–100], respectively. Conclusion: Baseline levels of TPOAb and TgAb may serve as markers for the risk of thyroid irAEs in cancer patients with solid malignancies who are planned to receive anti-tumor immunotherapy with ICIs.