Immune-related thyroid dysfunctions during anti PD-1/PD-L1 inhibitors: new evidence from a single centre experience

Abstract

The role of anti-thyroid peroxidase antibodies (anti-TPO Abs) in the development of abnormal thyroid function tests (DYSTHYR) during treatment with immune checkpoint inhibitors (ICIs) is not fully understood; moreover, controversial data exist about the relationship between ICI-related thyroid dysfunction (TD) and survival. We retrospectively analyzed the onset or the worsening of DYSTHYR in patients treated with programmed cell death protein-1 (PD-1) or its ligand (PD-L1) inhibitors between 2017 and 2020. In patients without previous TD, we focused on the association between baseline anti-TPO Abs level and DYSTHYR. Furthermore, the relationship between DYSTHYR and progression-free survival (PFS) or overall survival (OS) was explored. We included 324 patients treated with anti PD-1 (95.4%) or anti PD-L1 inhibitors. After a median of 3.3 months, DYSTHYR was registered in 24.7%, mostly hypothyroidism alone (17%). Patients with pre-existing TD (14.5% of the sample) were at higher risk of DYSTHYR compared to patients without previous TD (adjusted OR 2.44; 95% IC 1.26-4.74). In patients without known previous TD, high anti-TPO Abs level, even below the positivity cut-off, was a risk factor for developing DYSTHYR (adjusted OR 5.52; 95% IC 1.47-20.74). DYSTHYR was associated with a longer 12-month OS (87.3% vs 73.5%, p = 0.03); no statistically significant difference in terms of PFS was observed between the DYSTHYR+ and DYSTHYR- group. DYSTHYR is common during anti PD-1/anti PD-L1 treatment, especially in patients with pre-existing TD. In subjects without known previous TD, high anti-TPO Abs level at baseline can be a predictive biomarker of DYSTHYR. An improved OS is observed in patients with anti PD-1/anti PD-L1-induced DYSTHYR.

Keywords: Anti-thyroid peroxidase antibodies; Hypothyroidism; Immune checkpoint inhibitors; Survival; Thyrotoxicosis.