Endocrine-related adverse events following ipilimumab in patients with advanced melanoma: a comprehensive retrospective review from a single institution.
Endocrine-related adverse events following ipilimumab in patients with advanced melanoma: a comprehensive retrospective review from a single institution.
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DOI：
10.1530/erc-13-0499
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发表时间：
2014-04
影响因子：
3.9
通讯作者：
Fagin JA
中科院分区：
文献类型：
--
作者：
Ryder M;Callahan M;Postow MA;Wolchok J;Fagin JA
ipilimumab（一种阻断细胞毒性t淋巴细胞抗原4 （CTLA4）的抗体）的新型免疫检查点阻断正在彻底改变癌症治疗。然而，ipilimumab诱导有症状的，有时严重的内分泌免疫相关不良事件（irae），这些不良事件的识别和报道并不一致。本综述的目的是在一个高度专业化的免疫检查点阻断中心全面描述易普利姆单抗治疗后内分泌病变的发生率、表现和管理。我们对2007年至2013年临床试验中接受伊匹单抗治疗的黑色素瘤患者的内分泌irae进行了回顾性分析。该分析共纳入256例患者。我们回顾垂体、甲状腺和肾上腺相关激素测试结果，以及患者的x线研究和临床病史，以确定和描述垂体炎、甲状腺功能减退、甲状腺炎和肾上腺功能障碍的病例。伊匹单抗治疗后，垂体炎的总发病率为8%，甲状腺功能减退/甲状腺炎的总发病率为6%。原发性肾上腺功能障碍罕见。ipilimumab和nivolumab联合治疗，抗程序性细胞死亡1 （PDCD1，也称为PD1）受体抗体，与甲状腺炎或甲状腺功能减退发生率22%和垂体炎发生率9%相关。虽然内源性激素分泌很少恢复，但所有激素替代患者的症状缓解，特别是垂体炎的症状缓解。总之，我们观察到单独CTLA4阻断，特别是与PD1阻断联合，与症状性（有时是严重的）垂体炎和甲状腺功能障碍的风险增加有关。及时开始激素替代可逆转症状。临床试验中对内分泌干扰素的评价和报告应采用标准化的诊断标准和术语。
Novel immune checkpoint blockade with ipilimumab, an antibody blocking the cytotoxic T-lymphocyte antigen 4 (CTLA4), is revolutionizing cancer therapy. However, ipilimumab induces symptomatic, sometimes severe, endocrine immune-related adverse events (irAEs) that are inconsistently recognized and reported. The objective of this review was to comprehensively characterize the incidence, presentation, and management of endocrinopathies following ipilimumab therapy in a single center that is highly specialized in immune checkpoint blockade. We carried out a retrospective analysis of endocrine irAEs in melanoma patients receiving ipilimumab therapy in clinical trials between 2007 and 2013. A total of 256 patients were included in this analysis. We reviewed pituitary-, thyroid-, and adrenal-related hormone test results, as well as radiographic studies and the clinical histories of patients, to identify and characterize cases of hypophysitis, hypothyroidism, thyroiditis, and adrenal dysfunction. Following ipilimumab therapy, the overall incidence of hypophysitis was 8% and that of hypothyroidism/thyroiditis 6%. Primary adrenal dysfunction was rare. Therapy with a combination of ipilimumab and nivolumab, an anti-programmed cell death 1 (PDCD1, also called PD1) receptor antibody, was associated with a 22% incidence of either thyroiditis or hypothyroidism and a 9% incidence of hypophysitis. Symptomatic relief, in particular, for hypophysitis, was achieved in all patients with hormone replacement, although endogenous hormone secretion rarely recovered. In summary, we observed that CTLA4 blockade alone, and in particular in combination with PD1 blockade, is associated with an increased risk of symptomatic, sometimes severe, hypophysitis as well as thyroid dysfunction. Prompt initiation with hormone replacement reverses symptoms. Evaluation and reporting of endocrine irAEs in clinical trials should be done using standardized diagnostic criteria and terminology.