Thinking Critically About Classifying Adverse Events: Incidence of Pancreatitis in Patients Treated With Nivolumab plus Ipilimumab
Thinking Critically About Classifying Adverse Events: Incidence of Pancreatitis in Patients Treated With Nivolumab plus Ipilimumab
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DOI：
10.1093/jnci/djw260
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发表时间：
2017-04-01
影响因子：
10.3
通讯作者：
Postow, Michael A.
中科院分区：
文献类型：
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作者：
Friedman, Claire F.;Clark, Varina;Postow, Michael A.
不良事件通用术语标准 (CTCAE) 旨在记录化疗的不良反应，但现在也用于记录免疫相关不良事件 (irAE)。 CTCAE 对 irAE 的表征对于确定剂量限制毒性 (DLT) 以及因此确定研究药物的推荐 II 期剂量 (RP2D) 具有重要意义。在 nivolumab + ipilimumab 的 I 期试验中，脂肪酶无症状增加是通知 RP2D 的主要 DLT。我们对 119 名在纪念斯隆凯特琳癌症中心接受纳武单抗 + 伊匹单抗联合治疗的黑色素瘤患者进行了一项回顾性研究，以调查淀粉酶和/或脂肪酶无症状 3 级或以上升高与胰腺炎（一种已知的 irAE）之间的关系。在 119 名患者中，只有 2 例患有胰腺炎，占淀粉酶 3 级或更高水平的患者的 20%，脂肪酶 3 级或更高水平的患者占 6.3%，两种酶均达到 3 级或更高水平的患者占 20%。在新型免疫治疗药物的临床试验中应仔细考虑 CTCAE 的应用，特别是在对独立实验室值进行分级方面。
The Common Terminology Criteria for Adverse Events (CTCAE) were developed to document the adverse effects of chemotherapy but are now also used to document immune-related adverse events (irAE). Characterization of irAE by the CTCAE has implications for determining dose-limiting toxicity (DLT) and, consequently, the recommended phase II dose (RP2D) of investigational agents. In the phase I trial of nivolumab + ipilimumab, an asymptomatic increase in lipase was the primary DLT that informed the RP2D. We performed a retrospective study of 119 patients with melanoma who were treated at Memorial Sloan Kettering Cancer Center with the combination of nivolumab + ipilimumab to investigate the relationship between asymptomatic grade 3 or higher increases in amylase and/or lipase and pancreatitis, a known irAE. Of the 119 patients, there were only two cases of pancreatitis, representing 20% of patients with grade 3 or higher amylase, 6.3% of patients with grade 3 or higher lipase, and 20% of patients with grade 3 or higher elevations of both enzymes. The application of the CTCAE, especially in grading independent lab values, should be considered carefully in clinical trials of novel immunotherapeutic agents.