Characterizing Thyroid Hormone Replacement, Baseline Thyrotropin, and Survival in Immune Checkpoint Inhibitor-Associated Thyroid Dysfunction.

ICI-associated thyroid dysfunction developed in 15% of patients receiving immune checkpoint inhibitors.

• Of 811 included patients, 122 (15.0%) developed ICI-TD.
• Median follow-up was 19.2 months.
• Median age at ICI initiation was 64.8 years; women comprised 42.8% of the cohort.
• 28 patients with preexisting primary hypothyroidism were excluded from the 839 total patients evaluated.
• There were no significant differences in age, sex, race, malignancy type, or personal history of autoimmunity between patients who developed ICI-TD versus those who did not.

ICI-TD occurred most frequently after combination ICI therapy compared with CTLA-4 or PD-1/PD-L1 monotherapy.

• Combination ICI therapy was associated with ICI-TD in 32% of cases.
• The difference across ICI therapy types was statistically significant (p = 0.002).
• Comparison groups included CTLA-4 ICI monotherapy and PD-1/PD-L1 ICI monotherapy.

The levothyroxine dose required for overt hypothyroidism from ICI-TD was highest among hypothyroidism subgroups and is comparable to dosing for athyreotic hypothyroidism.

• The median levothyroxine dose was 1.41 mcg/kg/day in the overt hypothyroidism group.
• The authors concluded this dose is 'similar to athyreotic hypothyroidism.'
• This finding addresses questions about appropriate dosing for thyroid hormone replacement in this population.

Higher baseline pre-treatment TSH levels were associated with increased risk of developing ICI-TD, but baseline TSH lacked sufficient predictive ability.

• Patients with ICI-TD had a higher median pre-treatment log2(TSH) level of 1.2 (corresponding to TSH 2.3 mIU/L) versus 0.79 (corresponding to TSH 1.7 mIU/L) in those without ICI-TD (p = 0.008).
• The area under the curve was less than 0.6, indicating lack of predictive ability.
• The authors concluded 'there is no absolute baseline TSH value that accurately predicts ICI-TD in the clinical setting.'

The apparent survival benefit associated with ICI-TD was not confirmed after addressing immortal time bias and adjusting for other variables.

• Kaplan-Meier survival and log-rank tests were initially used to compare overall survival distributions between ICI-TD status groups.
• Cox regression models were subsequently used to address immortal time bias (ITB).
• After accounting for ITB and adjusting for other variables affecting patient outcomes, the survival benefit of ICI-TD was not apparent.
• The authors stated 'the link between ICI-TD and OS needs further validation after accounting for ITB.'

The study was a retrospective cohort of adult cancer patients receiving ICIs over a seven-year period at a single institution.

• The study period was December 1, 2012, to December 31, 2019.
• 811 patients were evaluated for new-onset ICI-TD after exclusions.
• The study design was a retrospective cohort study.
• Patients with preexisting primary hypothyroidism (n=28) were excluded.