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J Endocrinol Invest. 2018 May;41(5):549-556. doi: 10.1007/s40618-017-0772-1. Epub 2017 Oct 17.

Characterization and implications of thyroid dysfunction induced by immune checkpoint inhibitors in real-life clinical practice: a long-term prospective study from a referral institution.

Author information

1
Division of Oncological Endocrinology, Department of Medical Sciences, University of Turin, Turin, Italy. federica.guaraldi3@unibo.it.
2
Pituitary Unit, Department of Biomedical and Neuromotor Sciences (DIBINEM), IRCCS Institute of Neurological Sciences of Bologna, University of Bologna, Via Altura 3, 40139, Bologna, Italy. federica.guaraldi3@unibo.it.
3
Division of Dermatology, Department of Medical Sciences, University of Turin, Turin, Italy.
4
Division of Oncological Endocrinology, Department of Medical Sciences, University of Turin, Turin, Italy.
5
Hygiene, Public Health and Medical Statistics Unit, Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy.
6
Pituitary Unit, Department of Biomedical and Neuromotor Sciences (DIBINEM), IRCCS Institute of Neurological Sciences of Bologna, University of Bologna, Via Altura 3, 40139, Bologna, Italy.
7
Department of Health Sciences, "A. Avogadro" University of Eastern Piedmont, Novara, Italy.

Abstract

PURPOSE:

Autoimmune diseases are typically associated with immune checkpoints blockade. This study aims at assessing, in real-life clinical practice, the prevalence and impact of thyroid disorders induced by immune checkpoint inhibitors.

METHODS:

52 patients (30 F; age 61 ± 13 years) with advanced melanoma treated with ipilimumab (3 mg/kg i.v./3 weeks; 4 doses) were included. For disease progression, 29 (16 F) of them received nivolumab (3 mg/kg i.v./2 weeks) or pembrolizumab (2 mg/kg i.v./3 weeks). Thyroid function and autoimmunity were assessed before, after 6 weeks, at the end of ipilimumab, as well as before and every 3 months during nivolumab/pembrolizumab treatment.

RESULTS:

During ipilimumab, 7 (4 F) patients developed thyroid dysfunction (4 thyroiditis, 1 associated with hypothyroidism; 2 thyrotoxicosis in a previously euthyroid multinodular goiter; 1 hypothyroidism worsened). During PD1 inhibitors, 7 patients (3 F) developed hypothyroidism with severe manifestations in 6 of them; 3 patients suffered from euthyroid autoimmune thyroiditis from baseline, one after ipilimumab; 2 patients developed after transient thyrotoxicosis. Mean follow-up after anti-CTLA4 inhibitors treatment was 36 ± 28 months. Thyroid disorders occurred 45.1 ± 20.8 and 151 ± 67 days after the initiation of CTLA4 and PD1 inhibitors, respectively. Autoimmune disorders and BRAF mutation were associated with a better clinical response to CTLA4 followed by PD1 treatment.

CONCLUSIONS:

Immune checkpoint blockade is burdened by a high incidence of autoimmune thyroid dysfunction, which is often severe. Therefore, early and careful monitoring and, eventually, treatment are crucial to prevent the negative impact of thyroid dysfunction on the clinical outcome.

KEYWORDS:

Autoimmunity; CTLA4; Immune checkpoint inhibitors; Melanoma; PD1; Thyroid diseases

PMID:
29043574
DOI:
10.1007/s40618-017-0772-1
[Indexed for MEDLINE]

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