THYROID DYSFUNCTION, RECOVERY, AND PROGNOSIS IN MELANOMA PATIENTS TREATED WITH IMMUNE CHECKPOINT INHIBITORS: A RETROSPECTIVE REVIEW.

ABSTRACT

Objective: To describe thyroid dysfunction, factors associated with thyroid recovery, and survival in melanoma patients treated with immune checkpoint inhibitors that developed thyroid immune-related adverse events (irAEs). Methods: This was a retrospective study in a tertiary center from 2010-2017. We reviewed the charts of patients with melanoma that developed thyroid dysfunction after checkpoint inhibitor therapy. Cases with thyroid irAEs were grouped by recovery of thyroid function at 1 year. We collected a timeline of thyroid function tests, medication exposure, and survival and compared variables between the groups. We studied survival in comparison to a matched group without thyroid dysfunction. Results: A total of 186 melanoma patients received checkpoint inhibitors, and 17 (9%) had thyroid irAEs. Median time to abnormal thyroid-stimulating hormone was 38 days and followed a pattern of thyroiditis. Seven of 17 had thyroid recovery. In the no-recovery group, free thyroxine (T4) was often above 2 ng/dL (5/10 in no recovery, 0/7 in recovery; P = .04). In the recovery group, irAE grade was significantly lower, with 7/7 grade 1 (P = .004). Exposure to glucocorticoids was associated with recovery (3/10 in no recovery, 6/7 in recovery; P = .049). There was no difference in overall survival between the thyroid dysfunction group and controls, or between those that received glucocorticoids or not. Conclusion: Certain aspects of thyroid irAEs may correlate with thyroid recovery, including grade 1 thyroid irAEs, exposure to glucocorticoids, and peak free T4 levels less than 2 ng/dL. Thyroid irAEs did not appear to be associated with change in survival nor did exposure to glucocorticoids. Abbreviations ASCO = American Society of Clinical Oncology; CTLA-4 = cytotoxic T-lymphocyte-associated protein 4; irAE = immune-related adverse event; PD-1 = programmed cell death protein 1; T4 = thyroxine; TSH = thyroid-stimulating hormone.