Thyroid-Related Adverse Events in Melanoma Patients Treated with Pembrolizumab

Incidence of Thyroid-Related Adverse Events in Melanoma Patients Treated with Pembrolizumab: The Journal of Clinical Endocrinology &Metabolism, Early Release.







Jeroen de FiletteMD1, Yanina JansenMD2, Max SchreuerMD2, Hendrik EveraertMD, PhD3, Brigitte VelkeniersMD, PhD1, Bart NeynsMD, PhD2,*, and Bert BravenboerMD, PhD1,*



Address all correspondence and requests for reprints to: Jeroen de Filette,

Department of Endocrinology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel (VUB), Campus Jette, Laarbeeklaan 101, 1090 Brussels, Belgium

, Phone: +32 2 477 41 11, Fax: +32 2 477 68 00, Email: jdefilet@vub.ac.be.

*These authors share the senior authorship

DOI: http://ift.tt/2bO4xVs



Abstract

Context:

Immune checkpoint blockade is associated with endocrine-related adverse events. Thyroid dysfunction during pembrolizumab therapy, an anti-programmed cell death 1 receptor (PD-1) monoclonal antibody (mAb), remains to be fully characterized.

Objective:

To assess the incidence and characteristics of pembrolizumab-associated thyroid dysfunction.

Design and setting:

Thyroid function was monitored prospectively in melanoma patients who initiated pembrolizumab within an expanded access program at a referral oncology center. 18Fluorodeoxyglucose uptake on positron emission tomography/computed tomography (18FDG-PET/CT) was reviewed in cases compatible with inflammatory thyroiditis.

Patients:

99 patients with advanced melanoma (aged 26.3–93.6 years; 63.6% females) who received at least 1 administration of pembrolizumab.

Main Outcome Measures:

Patient characteristics, thyroid function (TSH, fT4), thyroid autoantibodies and 18FDG-PET/CT.

Results:

18 adverse events of thyroid dysfunction were observed in 17 patients. Thyrotoxicosis occurred in 12 patients of which 9 evolved to hypothyroidism. Isolated hypothyroidism was present in 6 patients. Levothyroxine therapy was required in 10 of 15 hypothyroid patients. Thyroid autoantibodies were elevated during thyroid dysfunction in 4 of 10 cases. Diffuse increased 18FDG uptake by the thyroid gland was observed in all 7 thyrotoxic patients who progressed to hypothyroidism.

Conclusions:

Thyroid dysfunction is common in melanoma patients treated with pembrolizumab. Hypothyroidism and thyrotoxicosis related to inflammatory thyroiditis are the most frequent presentations. Serial measurements of thyroid function tests are indicated during anti-PD-1 mAb therapy. Thyrotoxicosis compatible with inflammatory thyroiditis was associated with diffuse increased 18FDG uptake by the thyroid gland. The prospective role of thyroid autoantibodies should be further investigated together with the histopathological correlates.

Affiliations

1Department of Endocrinology,

2Medical Oncology and

3Nuclear Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel (VUB), Laarbeeklaan 101, 1090 Brussels, Belgium

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