Characterizing Thyroid Hormone Replacement, Baseline Thyrotropin, and Survival in Immune Checkpoint...

Area of Science:

• Endocrinology
• Oncology
• Immunology

Background:

• Immune checkpoint inhibitors (ICIs) are widely used cancer therapies.
• Thyroid dysfunction (TD) is a common side effect of ICI treatment.
• Predictive factors, optimal hormone replacement, and survival associations of ICI-TD require further clarification.

Purpose of the Study:

• To investigate predictors of new-onset thyroid dysfunction in patients receiving ICIs.
• To determine appropriate levothyroxine dosing for ICI-induced hypothyroidism.
• To evaluate the association between ICI-TD and overall survival (OS), accounting for immortal time bias (ITB).

Main Methods:

• Retrospective cohort study of 811 adult cancer patients treated with ICIs (2012-2019).
• Exclusion of patients with pre-existing hypothyroidism.
• Kaplan-Meier analysis, log-rank tests, and Cox regression models to assess OS and ITB.

Main Results:

• 15.0% of patients developed ICI-TD; it was more frequent with combination ICI therapy.
• Levothyroxine dose for overt hypothyroidism was 1.41 mcg/kg/day, similar to athyreotic hypothyroidism.
• Higher baseline TSH (upper normal range) associated with increased ICI-TD risk, but lacked predictive accuracy (AUC < 0.6).

Conclusions:

• Levothyroxine dosage for ICI-TD is comparable to that for athyreotic hypothyroidism.
• Upper normal range baseline TSH indicates increased ICI-TD risk, but cannot precisely predict it.
• The relationship between ICI-TD and OS requires further investigation, especially after addressing ITB.