The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network.
The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network.
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DOI：
10.1371/journal.pone.0053745
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Heinzerling LM
中科院分区：
文献类型：
--
作者：
Voskens CJ;Goldinger SM;Loquai C;Robert C;Kaehler KC;Berking C;Bergmann T;Bockmeyer CL;Eigentler T;Fluck M;Garbe C;Gutzmer R;Grabbe S;Hauschild A;Hein R;Hundorfean G;Justich A;Keller U;Klein C;Mateus C;Mohr P;Paetzold S;Satzger I;Schadendorf D;Schlaeppi M;Schuler G;Schuler-Thurner B;Trefzer U;Ulrich J;Vaubel J;von Moos R;Weder P;Wilhelm T;Göppner D;Dummer R;Heinzerling LM
伊匹单抗是一种细胞毒性T淋巴细胞抗原-4（CTLA-4）阻断抗体，已被批准用于治疗转移性黑色素瘤，并在高达64%的患者中诱导不良事件（AE）。用于管理常见的伊匹单抗诱导的AE的治疗算法已经导致发病率降低，例如由于肠穿孔。然而，随着伊匹单抗的应用越来越多，不太常见的AE谱正在扩大。严格识别和管理AE将降低药物诱导的发病率和成本，从而对药物的成本效益比产生积极影响。为了便于及时识别和充分管理，在19个皮肤癌中心分析了罕见AE的数据。筛选患者档案（n =752）中的罕见伊匹单抗相关AE。 共报告了120起AE，其中一些危及生命甚至致死，并按器官系统进行了总结，详细描述了最具指导意义的病例。记录了既往未报告的AE，如药疹伴嗜酸性粒细胞增多和全身症状（DRESS）、中枢神经系统肉芽肿性炎症和无菌性脑膜炎。障碍包括患者延迟报告症状和区分类固醇诱导的AE与类固醇治疗下的伊匹单抗诱导的AE。重要的是，尽管一些患者仅接受了四种推荐的伊匹单抗输注中的两种，但该患者人群的应答率较高，IV期黑色素瘤患者的肿瘤消退率为30.9%，肿瘤控制率为61.8%。这表明，ipilimumab诱导的抗肿瘤反应可以有一个早期发作，严重的自身免疫反应可能反映过度治疗。广泛的易普利姆玛诱导的AE要求医生和患者意识到降低发病率和治疗成本，并且真正的易普利姆玛成功取决于客观肿瘤反应和控制严重副作用。
Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers. Patient files (n = 752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientś delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment. The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects.
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DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
3.9
作者：
Blansfield, JA;Beck, KE;Sherry, RM
通讯作者：
Sherry, RM
影响因子：
158.5
作者：
Gogas, H;Ioannovich, J;Kirkwood, JM
通讯作者：
Kirkwood, JM
影响因子：
3.7
作者：
Maker, AV;Phan, GQ;Rosenberg, SA
通讯作者：
Rosenberg, SA
影响因子：
11.5
作者：
Kirkwood, John M.;Lorigan, Paul;Bulanhagui, Cecile A.
通讯作者：
Bulanhagui, Cecile A.