Endocrine Abstracts

Background: Immune checkpoint inhibitors (ICIs) have modified the outcome of several advanced malignancies. Thyroid dysfunctions (DYSTHYR) are the most common endocrine immune-related adverse events (IRAEs) during treatment with the programmed cell death protein-1 (PD-1) and its ligand (PD-L1) inhibitors. Data regarding predictive biomarkers enabling stratification of DYSTHYR risk are still limited.

Patients and methods: We retrospectively analyzed patients who started treatment with PD-1/PD-L1 inhibitors between 2017 and 2020 at Città della Salute e della Scienza Hospital (Department of Oncology). Both the onset of new DYSTHYR during ICI and the worsening of pre-existing DYSTHYR were recorded; patients with central hypothyroidism were excluded. In subjects without pre-existing hormonal thyroid alterations, it was evaluated the relationship between thyroid peroxidase antibody (Ab-TPO) level before the start of ICI and the onset of DYSTHYR during treatment. These patients were divided into two groups (MED-TPO+ and MED-TPO-) using the median Ab-TPO titer of the population as a cut-off value.

Results: In our cohort (median age 67 years, 70.7% males, 49.4% lung cancer, 95.4% anti PD-1 therapy), we observed a high frequency of DYSTHYR (80 out of 324 patients; 24.7%); thyrotoxicosis was detected in 7.7% of the population, while hypothyroidism occurred in 21% of subjects (after a median time of 1.8 and 3.7 months, respectively). Among cases with pre-existing thyroid hormonal alterations (14.5% of the sample), the worsening of DYSTHYR was found in 42.6% of cases after the start of ICI; the risk of DYSTHYR was significantly higher in comparison to patients without a thyroid disease history (OR 2.68 at univariate analysis, P 0.03). Baseline Ab-TPO levels were available for 97 patients (Ab-TPO median value 12 U/ml). Mean AbTPO level in the group with DYSTHYR during ICI (42.5 U/ml) was significantly higher than AbTPO titer in patients without DYSTHYR (16.1 U/ml, P=0.0003). DYSTHYR after the start of ICI occurred in 33.9% of MED-TPO+ patients vs 7.9% of MED-TPO- subjects (P=0.003); a significantly increased risk of developing DYSTHYR was observed in MED-TPO+ patients when compared to MED-TPO- cases (OR 5.98 at univariate analysis; P=0.007).

Conclusion: Our data confirm the high frequency of DYSTHYR (mostly hypothyroidism) during PD1/PD-L1 inhibitors. We observed a greater risk of DISTHYR during ICI in patients with pre-existing thyroid function alterations and in case of higher baseline Ab-TPO level. These results may help the oncologist to identify the patients who are most likely to require an endocrinologist consultation during ICIs.