Thyroid abnormalities following the use of cytotoxic T-lymphocyte antigen-4 and programmed death receptor protein-1 inhibitors in the treatment of melanoma.
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Date
2017-04-01ICR Author
Author
Morganstein, DL
Lai, Z
Spain, L
Diem, S
Levine, D
Mace, C
Gore, M
Larkin, J
Type
Journal Article
Metadata
Show full item recordAbstract
CONTEXT: Checkpoint inhibitors are emerging as important cancer therapies but are associated with a high rate of immune side effects, including endocrinopathy. OBJECTIVE: To determine the burden of thyroid dysfunction in patients with melanoma treated with immune checkpoint inhibitors and describe the clinical course. DESIGN AND PATIENTS: Consecutive patients with melanoma treated with either ipilimumab, nivolumab, pembrolizumab or the combination of ipilimumab and nivolumab were identified. Baseline thyroid function tests were used to exclude those with pre-existing thyroid abnormalities, and thyroid function tests during treatment used to identify those with thyroid dysfunction. RESULTS: Rates of overt thyroid dysfunction were in keeping with the published phase 3 trials. Hypothyroidism occurred in 13·0% treated with a programmed death receptor-1 (PD-1) inhibitor and 22·2% with a combination of PD-1 inhibitor and ipilimumab. Transient subclinical hyperthyroidism was observed in 13·0% treated with a PD-1 inhibitor, 15·9% following a PD-1 inhibitor, and 22·2% following combination treatment with investigations suggesting a thyroiditic mechanism rather than Graves' disease, and a high frequency of subsequent hypothyroidism. Any thyroid abnormality occurred in 23·0% following ipilimumab, 39·1% following a PD-1 inhibitor and 50% following combination treatment. Abnormal thyroid function was more common in female patients. CONCLUSION: Thyroid dysfunction occurs commonly in patients with melanoma treated with immune checkpoint inhibitors, with rates, including subclinical dysfunction, occurring in up to 50%.
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Subject
Humans
Melanoma
Thyroid Diseases
Antibodies, Monoclonal
Thyroid Function Tests
Adult
Aged
Middle Aged
Female
Male
CTLA-4 Antigen
Programmed Cell Death 1 Receptor
Ipilimumab
Nivolumab
Research team
Melanoma and Kidney Cancer
Language
eng
Date accepted
2016-12-20
License start date
2017-04
Citation
Clinical endocrinology, 2017, 86 (4), pp. 614 - 620
Publisher
WILEY