ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2017) 49 GP241 | DOI: 10.1530/endoabs.49.GP241

Thyroid-related adverse events in patients treated with Nivolumab

I Peiró1, L San Martín2, A Simó-Servat2, J Otero2, JC Ruffinelli3, E Nadal3, P Iglesias4, JJ Díez4 & C Villabona2

1Clinical Nutrition Unit, Institut Català d’Oncologia (ICO), Hospitalet de Llobregat, Spain; 2Department of Endocrinology, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Spain; 3Department of Oncology, ICO, Hospitalet de Llobregat, Spain; 4Department of Endocrinology, Hospital Ramón y Cajal, Madrid, Spain.

Introduction: Nivolumab is an antibody that binds to and blocks the activation of programmed-death-receptor 1(PD-1), promoting the activation of T-cells against tumor cells. Thyroid dysfunction (TD) is one of the most common immuno-related adverse events, with incidence up to 10% in patients treated with PD-1/PD-L1 blockade.

Objective: To report our experience of Nivolumab-TD in patients with advanced cancer.

Methods: All patients diagnosed of nivolumab-induced TD during 2016 were included. Data from thyroid function tests, autoimmunity and imaging study before and during nivolumab therapy were recorded.

Results: Twelve cancer patients (5 lung, 4 melanoma, 3 Hodgkin lymphoma) were evaluated. 75% women, mean age: 56.7 year (19–77). Ten patients were treated with nivolumab 3 mg/kg (with or without chemotherapy) every 15 days, 2 patients received combined immunotherapy (nivolumab 1 mg/kg plus ipilimumab 3 mg/kg). Three patients had previously well-controlled thyroid disease (1 overt primary hypothyroidism, 2 subclinical hypothyroidism). Baseline serum TSH and free thyroxine were evaluated in eleven patients, being normal in ten whereas one showed minimal subclinical hypothyroidism. During follow-up, 7 patients (58.3%) developed hyperthyroidism (4 overt and 3 subclinical). Six of them after cycle(C) 2, and 1 after C3. Thyroid antibodies were positive in 3 patients. One overt hyperthyroidism was treated with high dose steroids (prednisone 0.8 mg/kg per day) and nivolumab was temporarily withdrawn. Four of seven hyperthyroid patients became hypothyroid later, needing levothyroxine. Primary hypothyroidism occurred in 5 patients (41.7%) (3 overt and 2 subclinical), between C4-C7. Autoimmunity was positive in 3 hypothyroid patients. No patient discontinued nivolumab due to hypothyroidism.

Conclusions: In our series, hyperthyroidism is more frequent and appears earlier than hypothyroidism. A pattern consistent with a transient thyroiditis followed by hypothyroidism is seen in one-third of patients. Monitoring thyroid function at baseline and before each therapeutic cycle is warranted to detect and treat TD promptly.

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