Ipilimumab Therapy in Patients With Advanced Melanoma and Preexisting Autoimmune Disorders
Ipilimumab Therapy in Patients With Advanced Melanoma and Preexisting Autoimmune Disorders
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DOI：
10.1001/jamaoncol.2015.4368
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发表时间：
2016-02-01
期刊：
影响因子：
28.4
通讯作者：
Clark, Joseph I.
中科院分区：
文献类型：
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作者：
Johnson, Douglas B.;Sullivan, Ryan J.;Clark, Joseph I.
重要性伊匹单抗和其他免疫疗法是晚期黑色素瘤患者的有效治疗选择，但会导致频繁的免疫相关毒性反应。目的探讨自身免疫性疾病在晚期黑色素瘤患者中的安全性和有效性。设计、设置和参与者对2012年1月1日至2015年8月1日在9个学术三级转诊中心接受ipilimumab治疗的晚期黑色素瘤和既往自身免疫性疾病患者进行回顾性研究。数据分析进行于2015年8月24日。ExpoSURE Ipiimumab治疗。主要结果和措施安全性，根据自身免疫闪光和常规免疫相关不良事件(IrAEs)的频率，以及有效性，从应答率和总体生存的角度进行描述性评估。结果在接受ipilimumab治疗的30名患者中(17[57%]男性，中位年龄59.5[30-80]岁)，6名类风湿性关节炎，5名银屑病，6名炎症性肠道疾病，2名系统性红斑狼疮，2名多发性硬化症，2名自身免疫性甲状腺炎，7名其他疾病。13名患者(43%)在开始ipilimumab治疗时正在接受免疫抑制治疗，最常见的是小剂量强的松或羟氯喹。使用ipilimumab治疗，8名患者(27%)的自身免疫状况恶化，需要进行系统治疗；所有患者都接受了皮质类固醇治疗。10例(33%)发生常规3~5级irAEs，2例经激素或英夫利昔单抗治疗可逆。一名基线牛皮癣患者在报告症状前延迟一周后死于推测为免疫相关的结肠炎。15例(50%)患者既无自身免疫性疾病红斑，也无irAEs。6名患者出现客观应答(20%)，其中1名持续完全应答。结论与我们所知的相关，这是接受免疫检查点抑制剂治疗的既往自身免疫性疾病患者中规模最大的一组。Ipilimumab在临床上是活跃的，与自身免疫性疾病的恶化和传统的ipilimumab诱导的irAEs有关，当及时开始使用标准疗法时，这些疾病很容易得到控制。在这种情况下，可以考虑使用ipilimumab治疗，并进行警惕的临床监测。
IMPORTANCE Ipilimumab and other immune therapies are effective treatment options for patients with advanced melanoma but cause frequent immune-related toxic effects. Autoimmune diseases are common, and the safety and efficacy of ipilimumab therapy in patients with preexisting autoimmune disorders is not known.OBJECTIVE To determine the safety and efficacy of ipilimumab therapy in patients with advanced melanoma with preexisting autoimmune disorders.DESIGN, SETTING, AND PARTICIPANTS Retrospective review of patients with advanced melanoma and preexisting autoimmune disorders who received ipilimumab at 9 academic tertiary referral centers from January 1, 2012, through August 1, 2015. The data analysis was performed on August 24, 2015.EXPOSURE Ipilimumab therapy.MAIN OUTCOMES AND MEASURES Safety, in terms of frequency of autoimmune flares and conventional immune-related adverse events (irAEs), and efficacy, in terms of response rates and overall survival, were evaluated descriptively.RESULTS Of the 30 patients who received ipilimumab (17 [57%] male; median [range] age, 59.5 [30-80] y), 6 had rheumatoid arthritis, 5 had psoriasis, 6 had inflammatory bowel disease, 2 had systemic lupus erythematosus, 2 had multiple sclerosis, 2 had autoimmune thyroiditis, and 7 had other conditions. Thirteen patients (43%) were receiving immunosuppressive therapy at the time of initiation of ipilimumab therapy, most commonly low-dose prednisone or hydroxychloroquine. With ipilimumab treatment, 8 patients (27%) experienced exacerbations of their autoimmune condition necessitating systemic treatment; all were managed with corticosteroids. Conventional grade 3 to 5 irAEs occurred in 10 patients (33%) and were reversible with corticosteroids or with infliximab therapy in 2 cases. One patient with baseline psoriasis died of presumed immune-related colitis after a 1-week delay prior to reporting symptoms. Fifteen patients (50%) had neither autoimmune disease flares nor irAEs. Six patients experienced an objective response (20%), including 1 with a durable complete response.CONCLUSIONS AND RELEVANCE To our knowledge, this is the largest series of patients with preexisting autoimmune disease treated with immune checkpoint inhibitors. Ipilimumab was clinically active and was associated with exacerbations of autoimmune disease and conventional ipilimumab-induced irAEs that were readily manageable with standard therapies when started in a timely fashion. Ipilimumab therapy may be considered in this setting with vigilant clinical monitoring.