Elevated TSH Level, TgAb, and Prior Use of Ramucirumab or TKIs as Risk Factors for Thyroid Dysfunction in PD-L1 Blockade

Abstract

Background: Thyroid dysfunction is frequently caused by treatment with antiprogrammed cell death-1 ligand 1 antibodies (PD-L1-Abs) and anticancer drugs, including ramucirumab (RAM) and multitargeted tyrosine kinase inhibitors (multi-TKIs), which are often used prior to PD-L1-Ab treatment in cancer patients.

Methods: A total of 148 patients treated with PD-L1-Abs were evaluated for antithyroid antibodies at baseline and for thyroid function every 6 weeks for 24 weeks after treatment initiation and then were observed until the visits stopped.

Results: Of the 148 patients, 15 (10.1%) developed thyroid dysfunction after PD-L1-Ab treatment (destructive thyroiditis in 8 and hypothyroidism without preceding thyrotoxicosis in 7). The prevalence of an elevated thyroid-stimulating hormone (TSH) level at baseline (3/15 [20.0%] vs 4/133 [3.0%], P < .05), positive antithyroglobulin antibodies (TgAbs) at baseline (4/15 [26.7%] vs 5/133 [3.8%], P < .05) and prior treatment with RAM or multi-TKIs (3/15 [20.0%] vs 5/133 [3.8%], P < .05) were significantly higher in patients with vs without thyroid dysfunction. In a multivariate analysis, elevated TSH level at baseline, TgAb positivity at baseline, and prior treatment with RAM or multi-TKIs were significantly associated with the development of thyroid dysfunction, with ORs of 7.098 (95% CI 1.154-43.638), 11.927 (95% CI 2.526-56.316), and 8.476 (95% CI 1.592-45.115), respectively.

Conclusion: The results of this real-world study suggest that the risk of thyroid dysfunction induced by PD-L1-Abs can be predicted by the TSH level at baseline, TgAb positivity at baseline, and prior treatment with RAM or multi-TKIs.

Keywords: PD-L1; TKI; TgAb; hypothyroidism; irAE; ramucirumab; thyroglobulin; thyroiditis; thyrotoxicosis.