Long-term incidence of hypothyroidism and thyroiditis after CAR T-cell therapy versus standard chemotherapy in hematologic malignancies: A propensity-matched multi-institutional cohort study.

Abstract

11148 Background: Thyroid dysfunction is a common endocrine immune-related adverse event with modern cancer immunotherapies. Chimeric antigen receptor T-cell (CAR T) therapy is an adoptive cellular immunotherapy with expanding use in relapsed/refractory hematologic malignancies; its toxicity profile of cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome are well described, whereas endocrine sequelae are comparatively less characterized. Large-scale population analysis regarding the effect of CAR T therapy on thyroid function remains limited. As CAR T survivorship increases and indications broaden, defining long-term thyroid-related outcomes is essential in optimizing care. Methods: We performed a propensity-matched cohort study using the TriNetX Research Network (Jan 1, 2018–Jan 24, 2026). Adult, non-pregnant patients with DLBCL, PMBCL, follicular lymphoma, mantle cell lymphoma, multiple myeloma, or ALL were included. Patients receiving CAR T in addition to chemotherapy were compared with chemotherapy alone. Exclusions included prior thyroid disease/malignancy, central endocrine disorders, radiation therapy, bone marrow transplant, and baseline exposure to thyroid-active/thyroid-disrupting therapies (e.g., amiodarone, immune checkpoint inhibitors, tyrosine kinase inhibitors, interferons, immunomodulatory agents like lenalidomide). Propensity score matching balanced age, sex, race, malignancy type, baseline comorbidities, steroid exposure, and antipsychotic exposure. The primary outcome was new-onset hypothyroidism or thyroiditis; effect estimates are reported as ORs with 95% CIs. Results: Before propensity-score matching, there were 921 patients in the CAR T group and 24,426 in the chemo-only group. Post-matching, there were 878 CAR T patients and 879 chemo-only patients. Hypothyroidism or thyroiditis occurred in 16 patients in the CAR T group (1.822%) and in 21 patients in the chemo-only group (2.389%). Absolute risk difference was −0.567% (95% CI -1.909%, 0.776%; p = 0.4081) and the OR was 0.758 (95% CI 0.393, 1.463). No statistically significant difference in incidence was observed. Mean follow-up for CAR T after chemo and chemo-only groups were 670 and 964 days, respectively. Conclusions: In this large, multi-institutional propensity-matched real-world analysis with long-term follow-up, CAR T therapy after chemotherapy was not associated with increased incidence of hypothyroidism/thyroiditis compared with chemotherapy alone. These findings provide reassuring thyroid safety data, supporting the expanding use of CAR T as indications broaden. Future studies should evaluate thyroid outcomes by CAR T construct/target and characterize timing and severity to inform monitoring strategies.