Clinical Nutrition Unit, Institut Català d'Oncologia (ICO), L'Hospitalet de Llobregat, Avda Gran Via, 199-203, Barcelona, 08908, Spain.
Unit of Nutrition and Cancer, Biomedical Research Institute of Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
Endocrine. 2019 Jun;64(3):605-613. doi: 10.1007/s12020-019-01871-7. Epub 2019 Feb 25.
Nivolumab is a monoclonal antibody that blocks the activation of programmed death-1 receptor, promoting T-cell activation against cancer cells. Thyroid dysfunction (TD) is a common immune-related adverse event (irAE) induced by nivolumab. We report the prevalence, patterns and outcomes of nivolumab-induced TD among cancer patients in our center.
All patients treated with nivolumab during 2016 were included. We assessed thyroid function tests, thyroid autoimmunity, thyroid imaging, and clinical outcome during nivolumab therapy as well as overall survival (OS).
Seventy-three patients (55 with non-small-cell lung cancer [NSCLC], 9 with melanoma and 9 with Hodgkin lymphoma) were included. Median of follow up: 390.5 days. Seventeen patients (23.3%) developed TD during treatment. Thyrotoxicosis was reported in seven patients. Serum thyroid-stimulating hormone (TSH) nadir occurred after a median of 51 days (95% CI: 35-71). Thyroid antibodies were positive in three of the seven patients. Five of the seven hyperthyroid patients became hypothyroid later, and four of them required levothyroxine treatment. Primary hypothyroidism occurred in ten patients. Serum TSH peak occurred after a median of 110 days [95% CI: 85.2-197]. Thyroid autoimmunity was positive in one patient. In patients with NSCLC, TD was associated with better OS (HR = 0.4 [95% CI: 0.17-0.94]; p = 0.035).
TD induced by nivolumab is a common and heterogeneous irAE. Thyrotoxicosis develops earlier than hypothyroidism. A pattern consistent with a transient thyroiditis followed by hypothyroidism was observed in one-third of patients. Our results suggest that patients with NSCLC and nivolumab-induced TD might have better survival.
纳武利尤单抗是一种单克隆抗体，可阻断程序性死亡-1 受体的激活，从而促进 T 细胞对癌细胞的激活。甲状腺功能障碍（TD）是纳武利尤单抗引起的常见免疫相关不良事件（irAE）。我们报告了在我们中心接受纳武利尤单抗治疗的癌症患者中 TD 的发生率、模式和结局。
纳入 2016 年期间接受纳武利尤单抗治疗的所有患者。我们评估了甲状腺功能检查、甲状腺自身免疫、甲状腺成像以及纳武利尤单抗治疗期间的临床结局和总生存期（OS）。
共纳入 73 例患者（55 例非小细胞肺癌[NSCLC]、9 例黑色素瘤和 9 例霍奇金淋巴瘤）。中位随访时间：390.5 天。17 例（23.3%）患者在治疗期间发生 TD。7 例出现甲状腺毒症。血清促甲状腺激素（TSH）最低点出现在中位数 51 天（95%CI：35-71）。7 例甲状腺功能亢进症患者中 3 例甲状腺抗体阳性。5 例甲状腺功能亢进症患者后来出现甲状腺功能减退症，其中 4 例需要左甲状腺素治疗。10 例患者出现原发性甲状腺功能减退症。血清 TSH 峰值出现在中位数 110 天（95%CI：85.2-197）。1 例患者甲状腺自身免疫阳性。在 NSCLC 患者中，TD 与更好的 OS 相关（HR=0.4[95%CI：0.17-0.94]；p=0.035）。
纳武利尤单抗引起的 TD 是一种常见且异质性的 irAE。甲状腺毒症的发生早于甲状腺功能减退症。三分之一的患者观察到一致的模式，即短暂的甲状腺炎后出现甲状腺功能减退症。我们的结果表明，接受 NSCLC 和纳武利尤单抗治疗的患者可能有更好的生存。
