Immune-Related Thyroid Adverse Events Predict Response to PD-1 Blockade in Patients with Melanoma

Antibodies against programmed cell death protein-1 or its ligand (PD-(L)1) are a standard of care in melanoma; however, this treatment may cause immune-related adverse events. The aim of this study was to evaluate the immune-related thyroid adverse events (irTAEs) during anti-PD-1 therapy and analyze their influence on the overall survival rates in melanoma. We included 249 patients with metastatic melanoma treated in our institution between 2014 and 2021; the median age was 62 years (range: 17-90); 58% were males, and 37% of patients had the BRAF mutation. We included patients with a normal TSH at baseline and followed up with measurement of TSH levels during immunotherapy. In our group, 95 patients had a TSH outside the normal range: 63 not clinically significant and 32 with clinical symptoms of hypothyroidism. The 3-year overall survival rate was related to the irTAEs of clinical hypothyroidism, abnormal clinically not significant TSH, and euthyreosis at 56%, 43%, and 32%, respectively (p = 0.002). After adjusting the Cox model for potential confounding variables, clinically significant hypothyroidism was an independent prognostic factor with HR 0.51 (95% CI 0.29-0.87). In conclusion, the patients who developed clinically significant hypothyroidism requiring replacement therapy with L-thyroxin were the group who benefitted most from anti-PD-1 treatment.