Thyroid abnormalities following the use of cytotoxic T-lymphocyte antigen-4 and programmed death receptor protein-1 inhibitors in the treatment of melanoma
D L Morganstein, Z Lai, L Spain, Stefan Diem, D Levine, C Mace, M Gore & J Larkin
abstract
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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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citation
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Morganstein D L, Lai Z, Spain L, Diem S, Levine D, Mace C, Gore M,
Larkin J. Thyroid abnormalities following the use of cytotoxic
T-lymphocyte antigen-4 and programmed death receptor protein-1
inhibitors in the treatment of melanoma. Clin Endocrinol (Oxf) 2017;
86:614-620.
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type
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journal paper/review (English)
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date of publishing
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27-01-2017
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journal title
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Clin Endocrinol (Oxf) (86/4)
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ISSN electronic
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1365-2265
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pages
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614-620
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PubMed
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28028828
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DOI
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10.1111/cen.13297
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