Sex and interleukin-6 are prognostic factors for autoimmune toxicity following treatment with anti-CTLA4 blockade.
Sex and interleukin-6 are prognostic factors for autoimmune toxicity following treatment with anti-CTLA4 blockade.
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DOI：
10.1186/s12967-018-1467-x
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发表时间：
2018-04-11
影响因子：
7.4
通讯作者：
Chiarion-Sileni V
中科院分区：
文献类型：
--
作者：
Valpione S;Pasquali S;Campana LG;Piccin L;Mocellin S;Pigozzo J;Chiarion-Sileni V
Ipilimumab是一种用于转移性黑色素瘤患者的许可免疫疗法，在美国，作为根治性切除的高风险黑色素瘤的辅助治疗。ipilimumab的使用与典型但不可预测的副作用模式相关。本研究的目的是鉴定能够预测易普利姆玛相关毒性的临床特征和血液生物标志物。我们进行了一项前瞻性研究，旨在分析与接受伊匹单抗（3 mg/kg，q3 w）治疗的患者的免疫相关毒性相关的潜在临床和生物学标志物。我们招募了140名连续的黑色素瘤患者，他们接受了易普利姆玛治疗转移性疾病。使用了以下前瞻性收集的数据：患者特征、既往治疗、与肿瘤负荷或免疫炎症状态相关的循环生物标志物水平（乳酸脱氢酶、C-反应蛋白、β2-微球蛋白、血管内皮生长因子、白细胞介素-2、白细胞介素-6、S-100、碱性磷酸酶、转氨酶）和血细胞亚群（白细胞和淋巴细胞亚群）。采用Logistic回归进行多因素分析。在140例患者中，36例（26%）发生了严重不良事件，33例（24%）因严重毒性而停止治疗。在分析的免疫特征生物标志物中，只有白细胞介素-6与毒性风险相关。女性患者的免疫相关不良事件进一步增加。低基线血清白细胞介素-6水平（OR = 2.84，95%CI 1.34-6.03，P = 0.007）和性别女性（OR = 1.5，95%CI 1.06-2.16，P = 0.022）是免疫相关不良事件的显著和独立的危险因素。基线IL 6血清水平和女性性别与重度毒性的较高风险显著且独立相关，并且可以在临床实践中用于对接受伊匹单抗治疗的患者进行个性化毒性监测。本文的在线版本（10.1186/s12967-018-1467-x）包含补充材料，可供授权用户使用。
Ipilimumab is a licensed immunotherapy for metastatic melanoma patients and, in the US, as adjuvant treatment for high risk melanoma radically resected. The use of ipilimumab is associated with a typical but unpredictable pattern of side effects. The purpose of this study was to identify clinical features and blood biomarkers capable of predicting ipilimumab related toxicity. We performed a prospective study aimed at analyzing potential clinical and biological markers associated with immune-related toxicity in patients treated with ipilimumab (3 mg/kg, q3w). We enrolled 140 consecutive melanoma patients treated with ipilimumab for metastatic disease. The following prospectively collected data were utilized: patient characteristics, previous therapies, level of circulating biomarkers associated with tumour burden or immune-inflammation status (lactic dehydrogenase, C-reactive protein, β2-microglobulin, vascular endothelial growth factor, interleukin-2, interleukin-6, S-100, alkaline phosphatase, transaminases) and blood cells subsets (leukocyte and lymphocyte subpopulations). Logistic regression was used for multivariate analysis of data. Out of 140 patients, 36 (26%) experienced a severe adverse event, 33 (24%) discontinued treatment for severe toxicity. Among the immune-profile biomarkers analyzed, only interleukin-6 was associated with the risk of toxicity. Female patients had a further increase of immune-related adverse events. Low baseline interleukin-6 serum levels (OR = 2.84, 95% CI 1.34–6.03, P = 0.007) and sex female (OR = 1.5, 95% CI 1.06–2.16 P = 0.022) and were significant and independent risk factors for immune related adverse events. Baseline IL6 serum levels and female sex were significantly and independently associated with higher risk of severe toxicity and could be exploited in clinical practice to personalize toxicity surveillance in patients treated with ipilimumab. The online version of this article (10.1186/s12967-018-1467-x) contains supplementary material, which is available to authorized users.
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影响因子：
2.4
作者：
Barzey, Victor;Atkins, Michael B;Penrod, John R
通讯作者：
Penrod, John R
DOI：
10.1056/nejmoa1504030
发表时间：
2015-07-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Larkin J;Chiarion-Sileni V;Gonzalez R;Grob JJ;Cowey CL;Lao CD;Schadendorf D;Dummer R;Smylie M;Rutkowski P;Ferrucci PF;Hill A;Wagstaff J;Carlino MS;Haanen JB;Maio M;Marquez-Rodas I;McArthur GA;Ascierto PA;Long GV;Callahan MK;Postow MA;Grossmann K;Sznol M;Dreno B;Bastholt L;Yang A;Rollin LM;Horak C;Hodi FS;Wolchok JD
通讯作者：
Wolchok JD
DOI：
10.1158/1078-0432.ccr-15-2412
发表时间：
2016-06-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Martens A;Wistuba-Hamprecht K;Geukes Foppen M;Yuan J;Postow MA;Wong P;Romano E;Khammari A;Dreno B;Capone M;Ascierto PA;Di Giacomo AM;Maio M;Schilling B;Sucker A;Schadendorf D;Hassel JC;Eigentler TK;Martus P;Wolchok JD;Blank C;Pawelec G;Garbe C;Weide B
通讯作者：
Weide B
影响因子：
2.2
作者：
Hoejberg, Lise;Bastholt, Lars;Schmidt, Henrik
通讯作者：
Schmidt, Henrik
影响因子：
51.1
作者：
Eggermont, Alexander M. M.;Chiarion-Sileni, Vanna;Testori, Alessandro
通讯作者：
Testori, Alessandro