Multiple or Single Endocrine Abnormalities Associated With Immune Checkpoint Inhibitors.

Area of Science:

• Endocrinology
• Oncology
• Immunotherapy

Background:

• Immune checkpoint inhibitors (ICIs) can cause various endocrine abnormalities.
• The underlying mechanisms and impact of these endocrine dysfunctions on patient survival are not fully understood.
• Investigating the relationship between endocrine abnormalities and overall survival (OS) in patients treated with ICIs is crucial.

Purpose of the Study:

• To investigate the effect of single and multiple endocrine abnormalities on the overall survival (OS) of patients undergoing treatment with immune checkpoint inhibitors (ICIs).
• To identify risk factors associated with endocrine abnormalities in patients receiving ICIs.

Main Methods:

• A retrospective analysis of 12,978 patients treated with ICIs between 2014 and 2022 using the DeSC Japanese administrative claims database.
• Endocrine abnormalities were identified based on hormone replacement therapy (levothyroxine, hydrocortisone, insulin) and specific diagnoses like hypothyroidism post-thyroiditis and type 1 diabetes.
• Regression analyses were employed to assess risk factors for endocrine abnormalities and their impact on OS, adjusting for ICI treatment variables.

Main Results:

• Single and multiple endocrine abnormalities were detected in 12.0% and 1.4% of patients, respectively.
• Hypothyroidism combined with adrenal insufficiency was the most frequent combination (1.3%).
• Patients with single or multiple endocrine abnormalities exhibited significantly better OS compared to those without (P < .01).
• Multivariable analysis showed lower mortality in patients with endocrine abnormalities (aHR 0.39 for multiple, aHR 0.65 for single).
• Mortality was significantly lower in patients with multiple endocrine abnormalities compared to those with single abnormalities (aHR 0.56).

Conclusions:

• The development of endocrine abnormalities, especially multiple ones, in patients treated with ICIs is associated with improved overall survival.
• This finding suggests a potential survival benefit linked to ICI-induced endocrine dysfunctions.