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晚期黑色素瘤患者中免疫检查点抑制剂治疗诱导的免疫介导性结肠炎的成功治疗

Successful Treatment of an Immune-Mediated Colitis Induced by Checkpoint Inhibitor Therapy in a Patient with Advanced Melanoma.

作者信息

Paparoupa Maria, Stupperich Sophie, Goerg-Reifenberg Lisa, Wittig Andreas, Schuppert Frank

机构信息

Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Department of Gastroenterology, Endocrinology, Diabetology and General Medicine, Klinikum Kassel, Kassel, Germany.

出版信息

Case Rep Gastroenterol. 2020 Oct 29;14(3):554-560. doi: 10.1159/000511252. eCollection 2020 Sep-Dec.

DOI:10.1159/000511252
PMID:33250697
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7670360/
Abstract

Immune checkpoint inhibitors (ICIs) have been used as immunotherapeutic agents in several malignancies because of their ability to modify the T cell-mediated response against tumor cells. Dual checkpoint inhibition improves remission rates in patients with metastatic melanoma compared to monotherapy. However, a higher incidence of toxicity, including immune-related colitis, has been reported before. A 54-year-old female was diagnosed with malignant melanoma on her left upper arm. Because of progressive metastatic disease, a rescue therapy with nivolumab (Opdivo®) 1 mg/kg and ipilimumab (Yervoy®) 3 mg/kg was initiated and a clinical and radiological remission was achieved. Two weeks after completing the third cycle of the ICI therapy, the patient presented with persistent hemorrhagic diarrhea, nausea and abdominal pain. A diagnostic colonoscopy revealed multiple ulcerative lesions and hemorrhagic colitis of the sigmoid and rectum. Due to the ongoing treatment with nivolumab and ipilimumab, the diagnosis of a checkpoint inhibitor-induced colitis was made and immunosuppression with local and systemic steroids, such as mesalazine was initiated. In order to achieve a long-lasting steroids reduction, we decided to start with infliximab (Remicade® 5 mg/kg body weight i.v. every 2 weeks). Clinical remission was achieved and prednisolone could be subsequently discontinued. Infliximab, in combination with mesalazine, could successfully induce a long-lasting remission without steroids. The treatment of ICI-induced colitis did not lead to a reoccurrence of malignant melanoma after 2 years of follow-up.

摘要

免疫检查点抑制剂(ICIs)因其能够调节T细胞介导的抗肿瘤细胞反应,已被用作多种恶性肿瘤的免疫治疗药物。与单药治疗相比,双重检查点抑制可提高转移性黑色素瘤患者的缓解率。然而,此前已有报道称其毒性发生率较高,包括免疫相关结肠炎。一名54岁女性被诊断出左上臂患有恶性黑色素瘤。由于疾病进展为转移性,开始使用纳武单抗(欧狄沃®)1mg/kg和伊匹单抗(易普利姆玛®)3mg/kg进行挽救治疗,并实现了临床和影像学缓解。在完成ICI治疗的第三个周期两周后,患者出现持续性出血性腹泻、恶心和腹痛。诊断性结肠镜检查显示乙状结肠和直肠有多个溃疡性病变及出血性结肠炎。由于正在使用纳武单抗和伊匹单抗进行治疗,诊断为检查点抑制剂诱导的结肠炎,并开始使用局部和全身类固醇(如美沙拉嗪)进行免疫抑制。为了实现长期减少类固醇用量,我们决定开始使用英夫利昔单抗(类克®,体重5mg/kg静脉注射,每2周一次)。实现了临床缓解,随后泼尼松龙可以停药。英夫利昔单抗与美沙拉嗪联合使用可成功诱导无类固醇的长期缓解。对ICI诱导的结肠炎进行治疗后,经过2年随访,恶性黑色素瘤未复发。

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本文引用的文献

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Front Oncol. 2020 Feb 28;10:261. doi: 10.3389/fonc.2020.00261. eCollection 2020.
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Autoimmune hypophysitis secondary to therapy with immune checkpoint inhibitors: Four cases describing the clinical heterogeneity of central endocrine dysfunction.免疫检查点抑制剂治疗继发的自身免疫性垂体炎:4例描述中枢内分泌功能障碍的临床异质性
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Immunol Rev. 2023 Sep;318(1):96-109. doi: 10.1111/imr.13248. Epub 2023 Jul 25.
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Selective immune suppression using interleukin-6 receptor inhibitors for management of immune-related adverse events.使用白细胞介素 6 受体抑制剂进行选择性免疫抑制治疗免疫相关不良事件。
J Immunother Cancer. 2023 Jun;11(6). doi: 10.1136/jitc-2023-006814.
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Immune-mediated Gastritis in a Patient with metastatic Lung Cancer due to Therapy with the immune Checkpoint Inhibitor Pembrolizumab - Differences and Similarities in Comparison to "endogenous" autoimmune Type A Gastritis and a review of literature.一名转移性肺癌患者因使用免疫检查点抑制剂帕博利珠单抗治疗导致免疫介导性胃炎——与“内源性”自身免疫性A型胃炎相比的异同及文献综述
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Pharmacological Treatments Available for Immune-Checkpoint-Inhibitor-Induced Colitis.可用于免疫检查点抑制剂诱导的结肠炎的药物治疗方法。
Biomedicines. 2022 Jun 6;10(6):1334. doi: 10.3390/biomedicines10061334.
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Aliment Pharmacol Ther. 2019 Jun;49(12):1474-1483. doi: 10.1111/apt.15263. Epub 2019 Apr 29.
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BMJ Case Rep. 2019 Apr 3;12(4):e226481. doi: 10.1136/bcr-2018-226481.