Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Boston, Massachusetts.
MetroWest Medical Center, Framingham, Massachusetts.
Cancer Immunol Res. 2017 Dec;5(12):1133-1140. doi: 10.1158/2326-6066.CIR-17-0208. Epub 2017 Oct 27.
Thyroid disorders have emerged as one of the most common immune-related adverse events associated with anti-PD-1 monotherapy or combination anti-PD-1 and anti-CTLA-4 therapy. This study characterizes and compares the evolution of monotherapy and combination therapy-related thyroid disorders. We analyzed the dynamic evolution of thyroid disorders in 45 patients who developed thyroid disorders following treatment with either anti-PD-1 monotherapy or anti-PD-1 and anti-CTLA-4 combination therapy. The patients presented with thyrotoxicosis or hypothyroidism as the initial presentation of their thyroid disorder. Thyrotoxicosis as the initial presentation occurred in the majority of patients (93% and 56% of the patients receiving combination therapy and monotherapy, respectively). The onset pattern of the thyroid disorder was significantly different between the two groups ( = 0.01). Subsequently, 76% and 90% of the patients with thyrotoxicosis evolved to develop hypothyroidism in the combination and monotherapy groups, respectively. In the combination therapy and monotherapy groups, the median times to onset of thyrotoxicosis and hypothyroidism after first treatment were 21 and 63 days, and 31 and 68 days, respectively. The median time for transition from thyrotoxicosis to hypothyroidism was 42 days in both groups. Our study demonstrates that most thyroid disorders induced by either anti-PD-1 or combination anti-PD-1 and anti-CTLA-4 therapy are thyroiditis. The time to onset of thyrotoxicosis after treatment initiation and evolution of thyrotoxicosis to hypothyroidism was short, emphasizing the importance of close monitoring of thyroid function in these patients. .
甲状腺疾病已成为与抗 PD-1 单药或联合抗 PD-1 和抗 CTLA-4 治疗相关的最常见免疫相关不良事件之一。本研究对单药和联合治疗相关甲状腺疾病的演变进行了特征描述和比较。我们分析了 45 例接受抗 PD-1 单药或抗 PD-1 和抗 CTLA-4 联合治疗后发生甲状腺疾病的患者的甲状腺疾病的动态演变。这些患者的甲状腺疾病以甲状腺毒症或甲状腺功能减退症作为其初始表现。联合治疗组和单药治疗组中分别有 93%和 56%的患者以甲状腺毒症作为初始表现。两组间甲状腺疾病的发病模式有显著差异(=0.01)。随后,联合治疗组和单药治疗组中分别有 76%和 90%的甲状腺毒症患者进展为甲状腺功能减退症。在联合治疗组和单药治疗组中,首次治疗后发生甲状腺毒症和甲状腺功能减退症的中位时间分别为 21 天和 63 天,31 天和 68 天。两组中从甲状腺毒症向甲状腺功能减退症转变的中位时间均为 42 天。本研究表明,抗 PD-1 或联合抗 PD-1 和抗 CTLA-4 治疗引起的大多数甲状腺疾病都是甲状腺炎。治疗开始后甲状腺毒症的发病时间和甲状腺毒症向甲状腺功能减退症的演变时间较短,强调了这些患者密切监测甲状腺功能的重要性。