immune-related adverse effects (irAEs)

  • 文章类型: Case Reports
    免疫检查点抑制剂(ICI)治疗期间经常发生与免疫相关的不良反应(irAE)。在神经系统中,IRAE的发生率范围为0.1-12%,80%发生在ICI申请的前4个月内。对于神经系统的并发症,通过体征进行充分的诊断,症状,影像学和脑脊液。如果发生严重的irAE,ICIs应该停止,患者应该接受大剂量糖皮质激素治疗,免疫球蛋白,或全身支持的免疫吸附疗法。发生严重神经系统疾病的患者预后较差。
    在本文中,我们报道了2例抗程序性细胞死亡蛋白1(PD-1)单克隆抗体在初次诊断时诱发的脑病.我们的发现可能有助于临床医生区分由免疫疗法引起的脑病和其他神经系统疾病。病例1是一名24岁的男性患者,曾接受PD-1免疫疗法治疗嗅觉神经母细胞瘤。第6个疗程后,他开始发展为持续性癫痫,给予高剂量糖皮质激素和免疫吸附治疗后显著下降。根据他的病史和实验室检查结果,PD-1诱发的脑病是最可能的诊断。病例2是一名67岁的女性患者,曾接受PD-1/程序性死亡配体-1治疗肺腺癌。经过1个周期的治疗,她开始头痛,随着免疫治疗的继续,她的认知功能逐渐下降。
    这些病例报告显示难以区分PD-1诱发的脑病和其他神经系统疾病,尤其是副肿瘤神经综合征.如果治疗不当,病人的生命可能会受到威胁。因此,早期识别和早期治疗非常重要。
    UNASSIGNED: Immune-related adverse effects (irAEs) often occur during immune checkpoint inhibitor (ICI) therapy. In the nervous system, the incidence of irAEs ranges from 0.1-12%, with 80% occurring within the first 4 months of ICI application. For complications of the nervous system, adequate diagnosis is made by signs, symptoms, imaging and cerebrospinal fluid. If severe irAEs occur, ICIs should be discontinued and patients should be treated with high-dose glucocorticoids, immunoglobulins, or immunosorbent therapy with systemic support. Patients who develop severe neurologic irAEs have a poorer prognosis.
    UNASSIGNED: In this article, we report 2 cases of encephalopathy induced by anti-programmed cell death protein 1 (PD-1) monoclonal antibodies at the initial diagnoses. Our findings may help clinicians to differentiate between encephalopathy caused by immunotherapy and other neurological disorders. Case 1 was a 24-year-old male patient who had undergone PD-1 immunotherapy to treat olfactory neuroblastoma. After the 6th course of therapy, he began to develop persistent epilepsy, which decreased significantly after high doses of glucocorticoid and immunosorbent therapy were administered. Based on his medical history and laboratory examination results, PD-1-induced encephalopathy was the most likely diagnosis. Case 2 was a 67-year-old female patient who had been treated with PD-1/programmed death ligand-1 therapy for lung adenocarcinoma. She began to have headaches after 1 cycle of treatment, and her cognitive function gradually decreased with the continuation of immunotherapy.
    UNASSIGNED: These case reports show the difficulty in distinguishing PD-1-induced encephalopathy from other neurological disorders, especially paraneoplastic neurological syndromes. If not treated properly, patients\' lives may be endangered. Thus, early identification and early treatment are very important.
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  • 文章类型: Journal Article
    PD-1抑制剂,作为一种常用的免疫检查点抑制剂,通过阻断PD-1/PD-L1信号通路来激活T细胞并防止免疫逃逸。近年来,他们改变了癌症的治疗前景,由于显著延长患者的生存期和提高其生活质量的优势。然而,随之而来的不可预测的免疫相关不良反应(irAE)鼠疫临床医生,如结肠炎,甚至可能致命的事件,如肠穿孔和梗阻。因此,了解临床表现和分级标准,潜在机制,可用的不同疗法,可获取的生物标志物,风险分层的基础对管理至关重要。目前的证据表明,irAE可能是患者免疫治疗的临床益处的标志,因此,是否在irAE发作后停用PD-1抑制剂以及在irAE缓解后重新激发,需要进一步评估潜在的风险回报比,以及更多来自大规模前瞻性研究的数据来充分验证.最后,对PD-1抑制剂引起的罕见胃肠道毒性事件也进行了梳理。这篇综述提供了有关PD-1抑制剂引起的胃肠道毒性的可用数据的摘要。为了提高临床医生在日常实践中的意识,这样患者就可以安全地从治疗中受益。
    PD-1 inhibitors, as one of commonly used immune checkpoint inhibitors, enable T-cell activation and prevent immune escape by blocking the PD-1/PD-L1 signaling pathway. They have transformed the treatment landscape for cancer in recent years, due to the advantages of significantly prolonging patients\' survival and improving their life quality. However, the ensuing unpredictable immune-related adverse effects (irAEs) plague clinicians, such as colitis and even potentially fatal events like intestinal perforation and obstruction. Therefore, understanding the clinical manifestations and grading criteria, underlying mechanisms, available diverse therapies, accessible biomarkers, and basis for risk stratification is of great importance for the management. Current evidence suggests that irAEs may be a marker of clinical benefit to immunotherapy in patients, so whether to discontinue PD-1 inhibitors after the onset of irAEs and rechallenge after remission of irAEs requires further evaluation of potential risk-reward ratios as well as more data from large-scale prospective studies to fully validate. At the end, the rare gastrointestinal toxicity events caused by PD-1 inhibitors are also sorted out. This review provides a summary of available data on the gastrointestinal toxicity profile caused by PD-1 inhibitors, with the aim of raising clinicians\' awareness in daily practice, so that patients can safely benefit from therapy.
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  • 文章类型: Journal Article
    免疫治疗剂的开发改变了癌症治疗模式,具有更好的结果和更小的副作用。然而,有与之相关的不良事件。由于免疫系统的刺激增加,保护身体免受自身免疫反应的正常稳态机制可能会被破坏,导致多种副作用,称为免疫相关不良反应(irAE)。irAE可具有显著的相关发病率,并且在许多情况下导致停止治疗,对患者的病程具有不可预测的影响。很少有关键文章列出了irAE管理指南,为大多数常见irAE提供了一般的治疗算法。护士应了解与此类治疗相关的机制和不良事件。肿瘤科护士在识别irAE中起着至关重要的作用。IRAE可能涉及多个系统,因此,有必要根据这些情况尽快识别和管理这些不良事件。
    Development of immunotherapy agents has changed the cancer treatment paradigm with better outcomes and lesser side effects. Yet, there are adverse events associated with them. Owing to the increased stimulation of the immune system, the normal homeostatic mechanisms protecting the body from its own immune response can become disrupted, leading to a variety of side effects termed immune-related adverse effects (irAEs). irAEs can have significant associated morbidity and in many cases lead to discontinuation of therapies with unpredictable impact on the course of patients\' disease. Few key articles laying out guidelines for the management of irAEs provide general treatment algorithms for the majority of the common irAEs. Nurses should have knowledge of the mechanism and adverse events associated with such therapies. Oncology nurses have a crucial role in identification of irAEs. irAEs may involve multiple systems, and thus, it is necessary to identify and manage these adverse events according to the case these at soon as possible.
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  • 文章类型: Journal Article
    BACKGROUND: Durvalumab is a programmed cell death ligand 1 (PD-L1) inhibitor indicated for stage III, unresectable non-small cell lung cancer (NSCLC) consolidation therapy following concurrent platinum-based chemoradiation based on results of the PACIFIC trial. Safety data of durvalumab demonstrates an increased risk of immune-related adverse effects (irAEs), most notably pneumonitis. Pneumonitis is a serious and potentially fatal complication of immunotherapy. It is important to investigate the incidence of pneumonitis in clinical practice to evaluate the generalizability of published data. The objective of this study is to assess and characterize real-world incidence of pneumonitis in patients with NSCLC receiving durvalumab.
    METHODS: This retrospective study included patients who were initiated on durvalumab for unresectable stage III NSCLC from February 2018 through November 2019. The data analysis utilized descriptive statistics to determine the incidence of pneumonitis associated with durvalumab.
    RESULTS: Of the 83 patients who were evaluated, 21 patients (25.3%) experienced pneumonitis, with 5 cases (6%) being grade 3/4. Seven patients were re-challenged with durvalumab, while 14 patients permanently discontinued durvalumab. There were no clearly identifiable risk factors leading to an increased incidence of pneumonitis.
    CONCLUSIONS: The results of this study indicate that real-world incidence of pneumonitis in stage III NSCLC patients receiving durvalumab consolidation therapy is congruent with the incidence reported in the PACIFIC trial.
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  • 文章类型: Journal Article
    癌症免疫疗法为晚期人类癌症的医治带来了伟大的革命。靶向细胞毒性T淋巴细胞相关抗原4(CTLA-4)和程序性细胞死亡蛋白1途径(PD-1/PD-L1)的免疫检查点抑制剂(ICIs)在过去几年中已被广泛施用,并被证明在各种恶性肿瘤中具有前景。虽然一些患者从ICI中获益,其他人对这些疗法没有反应甚至产生耐药性。在响应者中,因此,治疗伴随着免疫相关的不良反应(irAE),它们的受影响器官是多种多样的,严重程度和时机。一些毒性是致命的并导致免疫疗法的中断。抗CTLA-4至抗PD-1/PD-L1免疫疗法的毒性特征与常规抗癌疗法不同。虽然他们的介绍可能是相似的。为了更好地帮助临床医生认识,监测和管理越来越多的正在接受ICI治疗的癌症患者的irAE,本文总结了FDA批准的ICIs,并侧重于(1)与ICIs相关的现有毒性证据,(2)发生的不良反应,(3)影响ICIs治疗肿瘤应答者的因素,(4)预测的生物标志物,(5)ICI治疗耐药的新的潜在机制。
    Cancer immunotherapy has brought a great revolution in the treatment of advanced human cancer. Immune checkpoint inhibitors (ICIs) that target cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death protein 1 pathway (PD-1/PD-L1) have been widely administrated in the past years and demonstrated promising in a variety of malignancies. While some patients show benefit from ICIs, others do not respond or even develop resistance to these therapies. Among the responders, the treatments are consequently accompanied with immune-related adverse effects (irAEs), which are diverse in their effected organs, degree of severity and timing. Some of the toxicities are fatal and result in discontinuance of immunotherapy. The toxicity profile from anti-CTLA-4 to anti-PD-1/PD-L1 immunotherapies is distinct from those caused by conventional anticancer therapies, though their presentation may be similar. In order to better help clinicians recognize, monitor and manage irAEs in a growing population of cancer patients who are receiving ICI therapy, this article summarizes the FDA approved ICIs and focuses on (1) existing toxic evidence related to ICIs, (2) occurrence of irAEs, (3) factors influencing tumor responders treated with ICIs, (4) predictive biomarkers of irAEs, and (5) new potential mechanisms of resistance to ICI therapy.
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