Characteristics of Immune-Related Thyroid Adverse Events in Patients Treated with PD-1/PD-L1 Inhibitors

• Main Authors: Jee Hee Yoon, A Ram Hong, Hee Kyung Kim, Ho-Cheol Kang
• Format: Article
• Language: English
• Published: Academya Publishing Co. 2021-04-01
• Series: Endocrinology and Metabolism
• Subjects: programmed cell death 1 receptor; immune checkpoint inhibitors; hypothyroidism; adverse effects
• Online Access: http://www.e-enm.org/upload/pdf/enm-2020-906.pdf

Background Thyroid immune-related adverse events (IRAEs) have been reported in patients treated with programmed cell death protein-1 (PD-1) and programmed cell death protein-ligand 1 (PD-L1) inhibitors. We investigated the incidence and clinical course of PD-1/PD-L1 inhibitor-induced thyroid IRAEs, and identified predictable clinical risk factors of thyroid IRAEs, in particular, overt hypothyroidism (OH). Methods We retrospectively reviewed the medical records of 325 cancer patients receiving PD-1/PD-L1 inhibitor in a tertiary referral center. Results A total of 50.5% (164/325) of patients experienced at least one abnormal thyroid function following PD-1/PD-L1 inhibitor. Eighty-four patients (51.2%) of them recovered to normal thyroid function during follow-up. In overall population, 25 patients (7.7%) required thyroid hormone replacement therapy due to PD-1/PD-L1 inhibitor-induced OH. Patients who progressed to OH showed significantly higher baseline thyroid stimulating hormone level and longer duration of PD-1/PD-L1 inhibitor therapy than those without thyroid dysfunction or OH (both P<0.001). Median time interval to the development of OH was 3 months after the therapy. OH was significantly associated with positive anti-thyroid peroxidase antibody at baseline and anti-thyroglobulin antibody during the therapy than those without thyroid dysfunction or OH (P=0.015 and P=0.005, respectively). We observed no patients with OH who were able to stop levothyroxine replacement after the cessation of PD-1/PD-L1 inhibitor therapy. Conclusion PD-1/PD-L1 inhibitor-induced thyroid dysfunctions are considerably reversible; however, OH is irreversible requiring levothyroxine replacement even after stopping the therapy. Positive thyroid autoantibodies may predict the progression to OH.