Clinical features of immune‑related thyroid dysfunction and its association with outcomes in patients with advanced malignancies treated by PD‑1 blockade

Abstract

Programmed cell death protein-1 (PD-1) blockade therapy has improved outcomes in the treatment of advanced cancers. The therapy is well-tolerated, although it occasionally causes immune-related adverse events (irAEs). Thyroid dysfunction is one of the most common irAEs seen. Our aim was to clarify the clinical characteristics of thyroid dysfunction induced by PD-1 blockade and its association with the therapeutic effect of the treatment in advanced cancers. A total of 174 patients who received nivolumab or pembrolizumab for metastatic or unresectable advanced cancers were included in this retrospective study. The patients were divided into two groups: The thyroid dysfunction group and the euthyroid group. In the present study, the clinical characteristics, the association with anti-thyroid antibodies, as well as the progression-free survival (PFS) and overall survival (OS) were estimated. An adjusted Cox proportional hazard regression model was used to evaluate prognostic factors for OS and PFS. This study showed that 25 out of 150 patients (16.7%) developed immune-related thyroid dysfunction. Hypothyroidism occurred in the early stage of the clinical course (median: 12 weeks); subsequently, 9 of the 25 patients underwent a transient period of hyperthyroidism, all with mild symptoms. The presence of positive anti-thyroid antibodies at baseline was significantly higher in the thyroid dysfunction group (13/22) than in the euthyroid group (18/100, P=0.0002). Moreover, PFS (median: 66 vs. 27 weeks, hazard ratio (HR): 0.50, 95% CI: 0.26-0.89, P=0.02) and OS (median 156 vs. 59 weeks, HR: 0.34, 95% CI: 0.13-0.75, P=0.01) were significantly longer in the thyroid dysfunction group than in the euthyroid group. Multivariable analysis also revealed that thyroid dysfunction was an independent prognostic factor for OS (HR: 0.42, 95% CI: 0.16-0.97, P=0.04). These findings may enable the early recognition and appropriate management of thyroid dysfunction, and help in maximizing the therapeutic effect of PD-1 blockade.

Case Report: Lymphocytosis Associated With Fatal Hepatitis in a Thymoma Patient Treated With Anti-PD1: New Insight Into the Immune-Related Storm

“…Overall, clinicians should be vigilant against irAE in thymoma patients treated with ICIs, due to its prompt onset and fulminant progression. Other evidence has already shown thyroid immune-mediated damage to be an early side effect preceding and paralleling the autoimmune phenomena (44,45). We confirm the above-mentioned clinical behavior.…”

Thyroid Dysfunction in Lung Cancer Patients Treated with Immune Checkpoint Inhibitors (ICIs): Outcomes in a Multiethnic Urban Cohort

“…The relationship between ICIs-related thyroid dysfunction and the treatment response has been a topic of research in a number of retrospective studies [ 13 , 26 , 27 , 48 , 49 , 50 , 51 , 52 ] ( Table 4 ). Notably, none of these studies employed a landmark analysis approach.…”

Quantitative Dynamic 18F-FDG PET/CT in Survival Prediction of Metastatic Melanoma under PD-1 Inhibitors

“…Interestingly, patients with higher FD on interim PET/CT showed significantly longer PFS, suggesting a positive survival effect of the heterogeneity of 18 F-FDG distribution in the thyroid during PD-1 blockade. Although the pathophysiological basis for these findings cannot be easily clarified, we note the documented association between the development of thyroid dysfunction and an improvement in survival of patients treated by PD-1 blockade [ 55 ]. Importantly, in a recently published meta-analysis, a significant association between the development of endocrine irAEs, among which thyroid dysfunction, and a favorable benefit on survival was highlighted [ 56 ].…”