Spectrum of Clinical Presentations, Imaging Findings, and HLA Types in Immune Checkpoint Inhibitor-Induced...

Area of Science:

• Oncology
• Immunology
• Endocrinology

Background:

• Hypophysitis is an immune-related adverse event (irAE) associated with immune checkpoint inhibitors (CPIs).
• CPIs, particularly CTLA-4 inhibitors, are known to cause hypophysitis, while PD-1/PD-L1 inhibitors are less commonly associated.
• Understanding the clinical, imaging, and genetic factors of CPI-induced hypophysitis (CPI-hypophysitis) is crucial for patient management.

Purpose of the Study:

• To investigate the clinical, imaging, and HLA characteristics of CPI-hypophysitis.
• To compare the presentation of hypophysitis induced by different types of CPIs.
• To identify potential genetic predispositions, such as HLA types, associated with CPI-hypophysitis.

Main Methods:

• Retrospective analysis of 49 patients with CPI-hypophysitis.
• Examination of clinical and biochemical data, pituitary magnetic resonance imaging (MRI).
• Association analysis with HLA typing in a subset of patients.

Main Results:

• Patients receiving CTLA-4 inhibitors experienced faster onset of hypophysitis and more frequent abnormal pituitary MRI findings compared to PD-1/PD-L1 inhibitor monotherapy.
• Male patients exposed to anti-CTLA-4 agents had a shorter time to hypophysitis onset than females.
• HLA type DQ0602 was significantly over-represented in patients with CPI-hypophysitis compared to the general Caucasian population.

Conclusions:

• The association with HLA DQ0602 suggests a genetic susceptibility to CPI-hypophysitis.
• The clinical presentation of CPI-hypophysitis is heterogeneous and influenced by CPI type, sex, and timing of onset.
• Further research into these factors is needed for a better mechanistic understanding of CPI-hypophysitis.