Endocrine Abstracts

Background: Immune checkpoint inhibitors (ICPIs) are indicated as treatment for metastatic renal cell carcinoma (RCC) and melanoma, among other malignancies. This group of agents is associated with immune-related adverse events (irAEs). We aimed to further investigate the association of immune-related thyroid disorders (irTDs) with clinical outcomes and mortality rates in patients with RCC or melanoma who were treated with ICPIs.

Methods: We retrospectively analyzed all RCC and melanoma patients with normal baseline thyroid function who were treated with ICPIs at the Tel Aviv Sourasky medical center from 2016 to 2022. Demographic, clinical, and laboratory parameters were extracted using a big data platform (MDclone, Israel).

Results: We identified 149 ICPI-treated patients with RCC, of whom 108 (72.5%) were male. The average age at RCC diagnosis was 65.5±10.6 years. Thyroid function abnormalities occurred in 42.3% (n=63) of ICPI-treated RCC patients. We analyzed 157 ICPI-treated patients with melanoma, of whom 92 (58.6%) were male. The average age at melanoma diagnosis was 68.5±13.2 years. Thyroid function abnormalities occurred in 49% (n=77) of ICPI-treated melanoma patients. Thyroid disorders in both RCC and melanoma ICPI-treated patients were due mostly to hypothyroidism (clinical/subclinical) or thyroiditis, with hyperthyroidism occurring in fewer than 10% of patients. Mortality rates were significantly lower in RCC patients with evidence of irTDs compared with those who had no thyroid abnormality (38.1% and 62.8%, respectively. P< 0.05). This difference in mortality rates remained significant in subgroup analysis of men with and without irTDs (30.8% and 63.8%, respectively. P< 0.05) but not in women. No significant difference in mortality rates was found in melanoma patients with and without thyroid dysfunction, including in a gender subgroup analysis.

Conclusion: irTDs in patients treated with ICPI may impact prognosis in RCC. This effect was not observed in our cohort of patients with melanoma. More studies are needed to further investigate and characterize the underlying mechanisms and clinical relevance.