Dynamics of immune-mediated thyroid dysfunction in patients with advanced renal cell carcinoma receiving checkpoint inhibitor therapy.

Abstract

e16071 Background: Checkpoint inhibitors (CPI) are quickly gaining relevance in the management of metastatic renal cell carcinoma (RCC). Treatment is generally well tolerated, but immune-induced thyroid dysfunction (TD) is reported in up to 10% of patients (pts) across trials. The dynamics of this phenomenon are undefined; hence there are no proposed standards for endocrine surveillance on therapy. Here we report on a cohort of RCC pts treated with CPI at Memorial Sloan Kettering Cancer Center with serial prospective assessment of thyroid function on therapy. Methods: Thyroid function tests (TFT) were assessed at baseline and serially on therapy. We recorded trends for hyper- and hypothyroidism and determined median time to development of TD by standard statistical methods. T4 replacement therapy was investigated by individual chart review. The association of TD with outcomes on CPI therapy was assessed by non-parametric tests. Results: Of 59 pts with serial TFT assessment, 20 were hypothyroid and 39 were euthyroid at baseline. 50% of previously hypothyroid pts required adjustment of T4 dosage. Thirteen of 39 euthyroid pts (36%) developed new TD requiring thyroid replacement. TD occurred early (median time to onset: 1.4 months, range 0.9-9.6), and in six of the 13 pts (46%), transient thyroiditis preceded hypothyroidism. None of the pts with thyroiditis required treatment, and the median duration from onset of thyroiditis to development of hypothyroidism was 1.5 months (range 0.7-2.8). All pts with hypothyroidism required replacement therapy; none required discontinuation of immunotherapy due to TD. TD was not associated with difference in objective response rate (fisher’s exact, p = 0.163), regression in target lesions (wilcoxon rank-sum, p = 0.135), or PFS (log rank p = 0.8214). Conclusions: TD is common in RCC pts receiving CPI therapy. In this cohort, onset of TD was early, thyroiditis was always transient, and no new cases were detected beyond 10 months. Confirming these findings in larger cohorts will provide meaningful data to guide management of TD when using this new class of agents outside of clinical trials.