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本文引用的文献

1
Checkpoint modulation in melanoma: an update on ipilimumab and future directions.黑色素瘤的检查点调节:伊匹单抗的最新进展及未来方向。
Curr Oncol Rep. 2013 Oct;15(5):500-8. doi: 10.1007/s11912-013-0337-1.
2
Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma.拉罗替尼(anti-PD-1)治疗黑色素瘤的安全性和肿瘤应答。
N Engl J Med. 2013 Jul 11;369(2):134-44. doi: 10.1056/NEJMoa1305133. Epub 2013 Jun 2.
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Ipilimumab for patients with advanced mucosal melanoma.伊匹单抗治疗晚期黏膜黑色素瘤患者。
Oncologist. 2013 Jun;18(6):726-32. doi: 10.1634/theoncologist.2012-0464. Epub 2013 May 28.
4
Patterns of onset and resolution of immune-related adverse events of special interest with ipilimumab: detailed safety analysis from a phase 3 trial in patients with advanced melanoma.依匹单抗治疗相关特殊关注免疫相关不良事件的发生和解决模式:晚期黑色素瘤患者 3 期试验的详细安全性分析。
Cancer. 2013 May 1;119(9):1675-82. doi: 10.1002/cncr.27969. Epub 2013 Feb 7.
5
Safety and activity of anti-PD-L1 antibody in patients with advanced cancer.抗 PD-L1 抗体在晚期癌症患者中的安全性和活性。
N Engl J Med. 2012 Jun 28;366(26):2455-65. doi: 10.1056/NEJMoa1200694. Epub 2012 Jun 2.
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Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.抗 PD-1 抗体在癌症中的安全性、活性和免疫相关性。
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The blockade of immune checkpoints in cancer immunotherapy.癌症免疫疗法中的免疫检查点阻断。
Nat Rev Cancer. 2012 Mar 22;12(4):252-64. doi: 10.1038/nrc3239.
8
Radiation-induced hypothyroidism in head and neck cancer patients: a systematic review.头颈部癌症患者放射性甲状腺功能减退症:系统评价。
Radiother Oncol. 2011 Apr;99(1):1-5. doi: 10.1016/j.radonc.2011.03.002. Epub 2011 Apr 1.
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Thyroid autoimmunity and ophthalmopathy related to melanoma biological therapy.甲状腺自身免疫和眼病与黑色素瘤生物治疗相关。
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10
Improved survival with ipilimumab in patients with metastatic melanoma.Ipilimumab 改善转移性黑色素瘤患者的生存。
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抗 PD1 治疗黏膜黑色素瘤:与严重甲状腺功能减退症和横纹肌溶解症相关的持久肿瘤反应。

Anti-PD1 following ipilimumab for mucosal melanoma: durable tumor response associated with severe hypothyroidism and rhabdomyolysis.

机构信息

Authors' Affiliations: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

出版信息

Cancer Immunol Res. 2014 Jan;2(1):15-8. doi: 10.1158/2326-6066.CIR-13-0146. Epub 2013 Oct 7.

DOI:10.1158/2326-6066.CIR-13-0146
PMID:24778161
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4006358/
Abstract

Treatment with fully human monoclonal antibodies against programmed death 1 (PD1) receptor has shown great promise for a number of advanced malignancies. Although inflammatory adverse events have been well described with anti-CTL antigen 4 (CTLA4) therapy, experience with the range of adverse effects of anti-PD1 remains comparatively limited. Here, we report on a patient with advanced mucosal melanoma who received four doses of MK-3475, a fully human monoclonal antibody against PD1, and experienced a durable near-complete response but developed severe hypothyroidism, rhabdomyolysis, and acute kidney injury. To our knowledge, this is the first case reported of a patient with advanced mucosal melanoma who responded to anti-PD1 therapy. With the promising antitumor effects of anti-PD1 in a wide array of tumors, we expect an increasing number of patients to be exposed to anti-PD1 therapies. Recognition of infrequent presentations of adverse events such as elevated creatine kinase levels and thyroid disorders in patients who receive anti-PD1 therapy is important.

摘要

治疗晚期恶性肿瘤的完全人源化单克隆抗体抗程序性死亡受体 1(PD1)显示出巨大的潜力。虽然抗细胞毒性 T 淋巴细胞相关抗原 4(CTLA4)治疗的炎症不良反应已得到很好的描述,但抗 PD1 治疗的一系列不良反应的经验相对有限。在这里,我们报告了一名晚期黏膜黑色素瘤患者,他接受了 4 剂 MK-3475(一种针对 PD1 的完全人源化单克隆抗体)治疗,经历了持久的近乎完全缓解,但出现严重甲状腺功能减退、横纹肌溶解和急性肾损伤。据我们所知,这是首例报道的晚期黏膜黑色素瘤患者对 PD1 治疗有反应的病例。随着抗 PD1 在多种肿瘤中的抗肿瘤作用的显著疗效,我们预计会有越来越多的患者接受抗 PD1 治疗。识别接受抗 PD1 治疗的患者中肌酸激酶水平升高和甲状腺疾病等罕见不良反应的表现非常重要。