Concurrent Pituitary and Thyroid Immune-Related Adverse Events after Immune Checkpoint Inhibitors Associated with...

Area of Science:

• Endocrinology
• Immunology
• Genetics

Background:

• Immune checkpoint blockade (ICB) therapy is crucial for cancer treatment.
• Immune-related adverse events (irAEs) can affect multiple organs during ICB.
• The co-occurrence of pituitary and thyroid irAEs is not well understood.

Purpose of the Study:

• To investigate the association between pituitary and thyroid dysfunction in patients receiving ICB.
• To identify genetic factors, specifically Human Leukocyte Antigen (HLA) haplotypes, associated with co-occurring pituitary and thyroid irAEs.

Main Methods:

• Prospective assessment of pituitary and thyroid function in 1,014 ICB-treated patients.
• Analysis of HLA alleles and haplotypes in patients with pituitary and/or thyroid irAEs.
• Validation of findings in a separate cohort of 92 patients with pituitary irAE.

Main Results:

• Thyroid irAE incidence was significantly higher in patients with pituitary irAE (30.9% vs. 11.3%).
• Specific HLA-DR15-associated haplotypes (DRB1*15:01-DQB1*06:02-DPB1*02:01 and DRB1*15:02-DQB1*06:01-DPB1*09:01) were significantly more frequent in patients with pituitary and/or thyroid irAEs.
• These genetic associations were confirmed in a validation cohort.

Conclusions:

• Pituitary and thyroid irAEs frequently co-occur during ICB treatment.
• HLA-DR15-associated haplotypes play a role in the development of co-occurring pituitary and thyroid irAEs.
• These findings suggest a shared genetic predisposition for these irAEs.