Post-CAR T-cell thyroid dysfunction: destructive thyroiditis identified through thyroid function monitoring in a...

Endocrine complications after chimeric antigen receptor (CAR) T-cell therapy remain poorly characterized. Thyroid dysfunction is well recognized during immune checkpoint inhibitor therapy, but thyroid function is not routinely incorporated into post-CAR T-cell toxicity assessment.

After observing an index case of destructive thyroiditis after CAR T-cell therapy, scheduled thyroid function monitoring was implemented in the subsequent 94 consecutive CAR T-cell recipients at our institution. This single-center study therefore included the index case and 94 consecutive post-index patients treated with axicabtagene ciloleucel, lisocabtagene maraleucel, or idecabtagene vicleucel.

Two patients developed transient thyrotoxicosis compatible with destructive thyroiditis, corresponding to an observed proportion of 2 of 95 patients [2.1%; exact 95% confidence interval (CI), 0.3-7.4%]. Both cases occurred among the 12 patients who experienced grade ≥2 cytokine release syndrome (CRS; 2 of 12; exact 95% CI, 2.1-48.4%). One case was supported by markedly reduced uptake on thyroid scintigraphy, whereas the other was considered probable destructive thyroiditis. Minor or transient thyroid function abnormalities that did not meet the diagnostic criteria for destructive thyroiditis were also observed.

Destructive thyroiditis may occur after CAR T-cell therapy and may be underrecognized because its manifestations overlap with other post-CAR T-cell inflammatory toxicities. The occurrence of both cases after grade ≥2 CRS represents a possible association and should be considered hypothesis-generating.