immune checkpoint inhibitors

免疫检查点抑制剂
  • 文章类型: Journal Article
    目的:比较PD-1和PD-L1抑制剂发生免疫相关性肺炎的风险,设计了荟萃分析。
    方法:通过两种不同的荟萃分析方法评估了PD-1和PD-L1抑制剂之间免疫相关性肺炎风险的差异,镜像配对和PRISMA指南。
    结果:共有88份报告用于荟萃分析,而32项研究用于镜像配对。PD-1和PD-L1抑制剂(单独使用或与化疗联合使用)都会增加发生免疫相关性肺炎的风险(P<0.00001;P<0.00001)。基于间接分析结果(子组分析),对照组化疗时,PD-L1诱导肺炎的风险弱于PD-1抑制剂(OR=3.33vs.5.43)或安慰剂(OR=2.53vs.3.19),差异无统计学意义(P=0.17;P=0.53)。对于基于镜像配对的荟萃分析,PD-1诱导肺炎的风险显著高于PD-L1抑制剂(OR=1.46,95CI[1.08,1.98],I2=0%,Z=2.47(P=0.01))。然而,这种差异并不显著,联合化疗时(OR=1.05,95CI[0.68,1.60],I2=38%,Z=0.21(P=0.84))。
    结论:PD-1和PD-L1抑制剂都会增加免疫相关性肺炎的风险,而PD-1诱导的肺炎风险明显高于PD-L1抑制剂。
    OBJECTIVE: To compare the risk of immune-associated pneumonitis between PD-1 and PD-L1 inhibitors, the meta-analysis was designed.
    METHODS: The difference in risk of immune-associated pneumonitis between PD-1 and PD-L1 inhibitors was assessed by two different meta-analysis methods, the Mirror-pairing and the PRISMA guidelines.
    RESULTS: A total of eighty-eight reports were used for meta-analysis, while thirty-two studies were used for the Mirror-pairing. Both PD-1 and PD-L1 inhibitors (used alone or combined with chemotherapy) increased the risk of developing immune-related pneumonitis (P < 0.00001; P < 0.00001). Based on indirect analyses results (subgroup analyses), the risk of PD-L1-induced pneumonitis was weaker than that of PD-1 inhibitors when the control group was chemotherapy (OR = 3.33 vs. 5.43) or placebo (OR = 2.53 vs. 3.19), while no obvious significant differences were found (P = 0.17; P = 0.53). For the Mirror-pairing-based meta-analysis, the risk of PD-1-induced pneumonitis was significantly higher than that of PD-L1 inhibitors (OR = 1.46, 95%CI [1.08, 1.98], I2 = 0%, Z = 2.47 (P = 0.01)). However, this difference was not significant, when they were combined with chemotherapy (OR = 1.05, 95%CI [0.68, 1.60], I2 = 38%, Z = 0.21 (P = 0.84)).
    CONCLUSIONS: Both PD-1 and PD-L1 inhibitors increased the risk of immune-related pneumonitis, while the risk of PD-1-induced pneumonitis was significantly higher than that of PD-L1 inhibitors.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    Immune checkpoint inhibitors (ICIs) have emerged as crucial therapeutic agents for various malignancies by activating the host immune system against tumor cells. However, many different types of skin adverse reactions may occur during its use, including eruption, pruritus, blistering, hypopigmentation, alopecia, and even severe cases, Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). These cutaneous immune-related adverse events (cirAEs) had a high incidence, which seriously affected patients\' quality of life and antitumor treatment decisions. Some severe cutaneous adverse reactions (SCARs) even endanger patients\' lives. Therefore, the Chinese Society of Dermatology, the Chinese Dermatologist Association of the Chinese Medical Doctor Association, the Dermatology Division of the Chinese Geriatrics Society, and other relevant experts jointly discussed and formulated the \'Chinese Expert Consensus on the Diagnosis and Treatment of Immune Checkpoint Inhibitor-Related Cutaneous Adverse Reactions\'. This consensus covers the name, epidemiology, pathogenesis, clinical features, classification and grading of cirAEs, principles of management and the re-initiation of ICIs. It aims to provide a more scientific and authoritative reference for the diagnosis and treatment of cirAEs in China in the future.
    免疫检查点抑制剂(ICIs)通过激活机体免疫系统抵御肿瘤细胞,目前已成为多种恶性肿瘤的重要治疗手段。但其使用过程中可能发生多种不同类型的皮肤不良反应,包括斑丘疹、瘙痒、水疱病变、色素减退和脱发等,严重者出现类似Steven-Johnson综合征/中毒性表皮坏死松解症(SJS/TEN)样表现。这些ICIs相关皮肤相关不良反应(cirAEs)发生率高,严重影响患者的生活质量和医师的治疗决策,部分严重的皮肤不良反应(SCARs)甚至危及生命。为此,中华医学会皮肤性病学分会、中国医师协会皮肤科医师分会、中国老年医学学会皮肤医学分会和其他相关领域的专家共同讨论并制订了《免疫检查点抑制剂相关皮肤不良反应诊治中国专家共识(2024版)》。此共识包括cirAEs的命名与流行病学、发病机制、临床特征、分类分级、诊断依据、治疗策略与ICIs的重启治疗等,旨在为中国cirAEs的诊治提供更科学、更权威的参考依据。.
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  • 文章类型: Journal Article
    对肿瘤-免疫相互作用的理解和操作的快速发展导致了对非小细胞肺癌患者的免疫疗法的批准。某些免疫检查点抑制剂治疗需要使用伴随诊断,但是方法的可变性导致了在实践中测试选择和实施的不确定性。
    为了制定免疫疗法/免疫调节生物标志物检测的循证指南建议,包括程序性死亡配体-1(PD-L1)和肿瘤突变负荷(TMB),肺癌患者。
    美国病理学家学会召集了一个非小细胞肺癌和生物标志物检测专家小组,根据美国国家医学科学院建立的值得信赖的临床实践指南标准,制定基于证据的建议。进行了系统的文献综述,以解决8个关键问题。使用建议评估的等级,发展,和评估(等级)方法,建议是从现有证据中创建的,证据的确定性,以及“从等级证据到决策框架”中定义的关键判断。
    制定了六项建议声明。
    本指南总结了在晚期非小细胞肺癌患者中使用PD-L1表达和TMB测试进行免疫检查点抑制剂治疗选择的当前理解和障碍,并提出了在临床环境中进行PD-L1和TMB测试的循证建议。
    UNASSIGNED: Rapid advancements in the understanding and manipulation of tumor-immune interactions have led to the approval of immune therapies for patients with non-small cell lung cancer. Certain immune checkpoint inhibitor therapies require the use of companion diagnostics, but methodologic variability has led to uncertainty around test selection and implementation in practice.
    UNASSIGNED: To develop evidence-based guideline recommendations for the testing of immunotherapy/immunomodulatory biomarkers, including programmed death ligand-1 (PD-L1) and tumor mutation burden (TMB), in patients with lung cancer.
    UNASSIGNED: The College of American Pathologists convened a panel of experts in non-small cell lung cancer and biomarker testing to develop evidence-based recommendations in accordance with the standards for trustworthy clinical practice guidelines established by the National Academy of Medicine. A systematic literature review was conducted to address 8 key questions. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, recommendations were created from the available evidence, certainty of that evidence, and key judgments as defined in the GRADE Evidence to Decision framework.
    UNASSIGNED: Six recommendation statements were developed.
    UNASSIGNED: This guideline summarizes the current understanding and hurdles associated with the use of PD-L1 expression and TMB testing for immune checkpoint inhibitor therapy selection in patients with advanced non-small cell lung cancer and presents evidence-based recommendations for PD-L1 and TMB testing in the clinical setting.
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  • 文章类型: Journal Article
    BACKGROUND: Renal cell carcinoma is the third most common tumor among urological tumors. In Germany more than 14,000 people are affected every year. The sex ratio is 2/3 men and 1/3 women.
    OBJECTIVE: The S3 guideline is intended to provide all disciplines dealing with renal cell carcinoma with the current status of diagnostics, therapy and follow-up care of the patients with this tumor.
    METHODS: The first version of the German guideline on renal cell carcinoma was published in 2015. The development was carried out at S3 level, which means that a structured, evidence-based literature search was carried out, recommendations and statements were developed in topic-related working groups and were approved by an interdisciplinary group of officials elected by the different medical societies. The chapters were gradually revised in 2017, 2020 and 2021 to reflect new aspects. This article provides information about the most important innovations of the most recent update from 2023.
    RESULTS: In the epidemiology subsection, the substance trichlorethene has been added as a risk factor for the development of renal cell carcinoma. While there were no new data on neoadjuvant therapy, the checkpoint inhibitor pembrolizumab was the first substance to demonstrate improved disease-specific and overall survival in the adjuvant situation. The combination nivolumab plus cabozantinib and lenvatinib plus pembrolizumab were included in the chapter on systemic therapy for metastatic clear cell renal cell carcinoma. New are the chapters on non-clear cell renal cell carcinoma and hereditary tumors.
    CONCLUSIONS: The S3 guideline provides a structured, evidence-based overview of all aspects of renal cell carcinoma.
    UNASSIGNED: HINTERGRUND: Das Nierenzellkarzinom (NCC) ist der dritthäufigste maligne Tumor unter den urologischen Tumoren. In Deutschland erkranken mehr als 14.000 Menschen pro Jahr. Das Geschlechterverhältnis beträgt zwei Drittel Männer und ein Drittel Frauen.
    UNASSIGNED: Die S3-Leitlinie soll allen mit dem NCC befassten Fachdisziplinen den aktuellen Stand zur Diagnostik, Therapie und Nachsorge des Tumors vermitteln.
    METHODS: Die Erstfassung der deutschen Leitlinie zum NCC erschien 2015. Die Erarbeitung erfolgte auf S3-Niveau, d. h. es erfolgte eine evidenzbasierte strukturierte Literaturrecherche. Die in themenbezogenen Kleingruppen erarbeiteten Empfehlungen und Statements wurden von der interdisziplinären Gruppe der Mandatsträger konsentiert. Als Living Guideline wurden 2017, 2020 und 2021 die Kapitel nach und nach entsprechend neuer Aspekte überarbeitet. Der vorliegende Artikel informiert über die wichtigsten Neuerungen der letzten Aktualisierung aus 2023.
    UNASSIGNED: Im Unterkapitel „Epidemiologie“ wurde die Substanz Trichlorethen neu als Risikofaktor für das Entstehen eines NCC aufgenommen. Während es zur neoadjuvanten Therapie keine neuen Daten gab, konnte mit dem Checkpoint-Inhibitor Pembrolizumab erstmals ein verbessertes krankheitsfreies und Gesamtüberleben in der adjuvanten Situation gezeigt werden. In das Kapitel zur Systemtherapie des metastasierten klarzelligen NCC wurden die Kombinationen Nivolumab und Cabozantinib sowie Lenvatinib und Pembrolizumab aufgenommen. Neu sind die Kapitel zu den nicht-klarzelligen NCC und den erblichen Tumoren.
    UNASSIGNED: Die S3-Leitlinie gibt einen strukturierten, evidenzbasierten Überblick über sämtliche Aspekte zum NCC.
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  • 文章类型: Journal Article
    随着越来越多的患者有资格获得免疫检查点抑制剂,免疫相关不良事件(irAEs)的发生率呈上升趋势.皮肤免疫相关不良事件(D-irAEs)是最常见且最早出现的,通常对患者有重要的下游后果。目前的指南在D-irAE的诊断标准方面缺乏明确性。该项目的目标是更好地定义D-irAE以进行识别,诊断,以及对这一重要疾病组的未来研究。该项目的目标是为D-irAE的方法制定共识指导,包括疾病定义和严重程度分级。知道肿瘤学家之间的共识,皮肤科医生,IRAE专家对可用性至关重要,我们形成了一个皮肤病性IRAE疾病定义小组。该小组由34名专家组成,包括肿瘤学家,皮肤科医生,风湿病学家,来自美国和国际上22个机构的过敏症专家/免疫学家。使用了改进的德尔菲共识过程,由小组成员进行两轮匿名评级,并举行两次虚拟会议讨论争议领域。小组成员对内容的可用性进行了评级,适当性,电子调查中9点量表的准确性,并提供自由文本评论。一个工作组汇总了调查答复,并将其纳入修订的定义。共识是基于数字评分,使用兰德/加州大学洛杉矶分校适当性方法和预先指定的定义。根据小组成员的反馈进行修订后,所有项目在第二轮评级中获得共识。对10种核心D-irAE诊断达成共识定义:ICI-白癜风,ICI-扁平苔藓,ICI-牛皮癣,ICI-exanthem,ICI-大疱性类天疱疮,ICI-Grover's,ICI-湿疹,ICI爆发的非典型鳞状增生,ICI-瘙痒无皮疹,和ICI侵蚀皮肤粘膜。对D-irAE的标准评估也达成了共识,必要时详细说明特定疾病的例外情况。每种疾病的描述包括疾病亚型的进一步细节,症状,支持性考试结果,和三个诊断确定性水平(确定,可能,并且可能)。这些共识驱动的疾病定义在多个学科的可用框架中标准化了D-irAE分类,并将成为未来工作的基础。鉴于代表小组对其准确性和可用性的共识,我们预计它们可以在临床和研究环境中广泛使用.
    With an increasing number of patients eligible for immune checkpoint inhibitors, the incidence of immune-related adverse events (irAEs) is on the rise. Dermatologic immune-related adverse events (D-irAEs) are the most common and earliest to manifest, often with important downstream consequences for the patient. Current guidelines lack clarity in terms of diagnostic criteria for D-irAEs. The goal of this project is to better define D-irAE for the purposes of identification, diagnosis, and future study of this important group of diseases.The objectives of this project were to develop consensus guidance for an approach to D-irAEs including disease definitions and severity grading. Knowing that consensus among oncologists, dermatologists, and irAE subspecialists would be critical for usability, we formed a Dermatologic irAE Disease Definition Panel. The panel was composed of 34 experts, including oncologists, dermatologists, a rheumatologist, and an allergist/immunologist from 22 institutions across the USA and internationally. A modified Delphi consensus process was used, with two rounds of anonymous ratings by panelists and two virtual meetings to discuss areas of controversy. Panelists rated content for usability, appropriateness, and accuracy on 9-point scales in electronic surveys and provided free text comments. A working group aggregated survey responses and incorporated them into revised definitions. Consensus was based on numeric ratings using the RAND/UCLA Appropriateness Method with prespecified definitions.Following revisions based on panelist feedback, all items received consensus in the second round of ratings. Consensus definitions were achieved for 10 core D-irAE diagnoses: ICI-vitiligo, ICI-lichen planus, ICI-psoriasis, ICI-exanthem, ICI-bullous pemphigoid, ICI-Grover\'s, ICI-eczematous, ICI-eruptive atypical squamous proliferation, ICI-pruritus without rash, and ICI-erosive mucocutaneous. A standard evaluation for D-irAE was also found to reach consensus, with disease-specific exceptions detailed when necessary. Each disorder\'s description includes further details on disease subtypes, symptoms, supportive exam findings, and three levels of diagnostic certainty (definite, probable, and possible).These consensus-driven disease definitions standardize D-irAE classification in a useable framework for multiple disciplines and will be the foundation for future work. Given consensus on their accuracy and usability from a representative panel group, we anticipate that they can be used broadly across clinical and research settings.
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  • 文章类型: Journal Article
    韩国妇科肿瘤学会管理宫颈癌实践指南的第五次修订版纳入了最新的研究结果和基于2020年发布的4.0版本的治疗策略的变化。每个关键问题都是通过关注宫颈癌领域的最新显着见解和重要的当代问题来开发的。评估了这些问题的重要性和对当前治疗的影响,并由发展委员会通过投票最终确定。选择的关键问题如下:免疫检查点抑制剂作为复发或转移性宫颈癌一线或二线治疗的有效性和安全性;早期宫颈癌微创根治性子宫切除术的肿瘤学安全性;局部晚期宫颈癌同步放化疗后辅助全身治疗的有效性和安全性;前哨淋巴结定位术与盆腔淋巴结清扫术相比的肿瘤学安全性。的建议,方向,本指南的优势是基于系统评价和荟萃分析,并最终通过公开听证会和外部审查得到确认。在这项研究中,我们描述了修订后的宫颈癌管理实践指南.
    This fifth revised version of the Korean Society of Gynecologic Oncology practice guidelines for the management of cervical cancer incorporates recent research findings and changes in treatment strategies based on version 4.0 released in 2020. Each key question was developed by focusing on recent notable insights and crucial contemporary issues in the field of cervical cancer. These questions were evaluated for their significance and impact on the current treatment and were finalized through voting by the development committee. The selected key questions were as follows: the efficacy and safety of immune checkpoint inhibitors as first- or second-line treatment for recurrent or metastatic cervical cancer; the oncologic safety of minimally invasive radical hysterectomy in early stage cervical cancer; the efficacy and safety of adjuvant systemic treatment after concurrent chemoradiotherapy in locally advanced cervical cancer; and the oncologic safety of sentinel lymph node mapping compared to pelvic lymph node dissection. The recommendations, directions, and strengths of this guideline were based on systematic reviews and meta-analyses, and were finally confirmed through public hearings and external reviews. In this study, we describe the revised practice guidelines for the management of cervical cancer.
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  • 文章类型: Letter
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  • 文章类型: Journal Article
    免疫检查点抑制剂(ICIs)提高了生存率,并越来越多地用于癌症。然而,ICIs的使用可能受到免疫相关不良事件(irAE)的限制,如ICI诱导的糖尿病(ICI-DM)。本研究的目的是表征ICI-DM患者和现实世界对指南的依从性。
    本研究对2018年7月至2022年10月南京医科大学第一附属医院ICI-DM患者的电子病历进行回顾性分析。
    34.8%(8/23)的患者在每个治疗周期监测血糖。严格血糖监测组重度糖尿病酮症酸中毒(DKA)患者比例低于非严格血糖监测组(16.7%vs.55.6%,p=0.049)。78.3%(18/23)的高血糖患者首先去了非内分泌学家,但95.7%的患者随后被转诊至内分泌学家.20例患者进行了区分高血糖病因的测试,20%的患者谷氨酸脱羧酶抗体(GADA)阳性,55%,C肽<3.33pmol/L。观察到其他ICI引起的内分泌疾病的高筛查率,并且一半的ICI-DM患者发生其他内分泌腺irAE,最常见的是甲状腺炎。此外,5例患者出现非内分泌严重不良事件(SAE).12例(52.2%)患者因ICI-DM退出ICI。ICI-DM患者继续和中断组的肿瘤进展时间长于停药组(333.5±82.5天vs.183.1±62.4天,p=0.161)。根据指南,只有17.4%的ICI-DM患者得到了完全治疗。因此,本研究提出了一种筛查,诊断,和实际实践中ICI-DM的管理算法。
    本研究报告了单个研究所描述的最多ICI-DM病例,提供对现实世界ICI-DM管理指南依从性的洞察,并强调ICI-DM管理中的临床挑战。
    Immune checkpoint inhibitors(ICIs) have improved survival and are increasingly used for cancer. However, ICIs use may be limited by immune-related adverse events (irAEs), such as ICI-induced diabetes mellitus(ICI-DM). The objective of the present study was to characterize ICI-DM patients and real-world adherence to guidelines.
    The present study was a retrospective review of electronic records of ICI-DM patients at the First Affiliated Hospital of Nanjing Medical University between July 2018 and October 2022.
    34.8% (8/23)patients monitored blood glucose in every treatment cycle. The proportion of patients with severe diabetic ketoacidosis(DKA) was lower in the tight glycemic monitoring group than the non-tight glycemic monitoring group (16.7% vs. 55.6%, p = 0.049). 78.3%(18/23) patients with hyperglycemia visited a non-endocrinologist first, but 95.7% of patients were then referred to an endocrinologist. Twenty patients were tested for distinguishing the etiology of hyperglycemia and 20% patients with positive glutamic acid decarboxylase antibody(GADA), 55% with C-peptide <3.33pmol/L. High screening rates for other ICI-induced endocrinopathies were observed and half of the patients with ICI-DM developed other endocrine gland irAEs, with the most common being thyroiditis. Moreover, five patients developed non-endocrine serious adverse events(SAEs). Twelve (52.2%) patients were withdrawn from ICI due to ICI-DM. The time to progression of tumor in ICI-DM patients in the continue and interruption group was longer than in the withdrawal group (333.5 ± 82.5 days vs. 183.1 ± 62.4 days, p = 0.161). Only 17.4% of ICI-DM patients were completely managed according to guidelines. Thus, the present study proposed a screening, diagnosis, and management algorithm for ICI-DM in real-world practice.
    The present study reported the largest number of ICI-DM cases described in a single institute, providing insight into real-world ICI-DM management guideline adherence and highlighting the clinical challenges in ICI-DM management.
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