pembrolizumab

派姆单抗
  • 文章类型: Case Reports
    肺泡软组织肉瘤(ASPS)是一种罕见的恶性肿瘤,表现为生长缓慢的软组织肿块,常伴有远处转移。预后是可变的,转移性疾病完全缓解的报道很少。我们的患者在17岁时被诊断为转移性ASPS,原发性前臂病变并转移到肺部。她接受了前臂肿块的手术切除,然后辅助化疗和放疗靶向肺转移。在接下来的十年里,她有一个复杂的治疗过程。尽管接受了舒尼替尼治疗,但她的疾病仍在缓慢进展,帕唑帕尼,以及多西他赛和吉西他滨的组合。我们最终用免疫检查点抑制剂(ICIs)治疗她。Pembrolizumab,最初与贝伐单抗联合使用,后来作为单药治疗,导致显著的肿瘤缩小,尤其是肺部病变,在头三个月内。随后的影像学报告在15个月内完全缓解,并且在她的三年随访中没有疾病复发。我们的病例突出了极少数报道的在ICIs治疗后转移性ASPS完全缓解的病例之一。ICI可以为晚期ASPS的疾病缓解提供希望,一种罕见的恶性肿瘤,过去证明很难成功治疗。需要进行更多的研究来进一步评估疗效和成功治疗的任何相关预测因素。
    Alveolar soft part sarcoma (ASPS) is a rare malignant tumor that manifests as a slow-growing soft tissue mass and frequently presents with distant metastasis. The prognosis is variable, and complete remission of metastatic disease has rarely been reported. Our patient was diagnosed with metastatic ASPS at the age of 17, with a primary forearm lesion and metastasis to the lungs. She underwent surgical resection of her forearm mass, followed by adjuvant chemotherapy and radiation to target the lung metastasis. Over the next decade, she had a complicated course of treatment. Her disease continued to slowly progress despite treatment with sunitinib, pazopanib, and a combination of docetaxel and gemcitabine. We eventually treated her with immune checkpoint inhibitors (ICIs). Pembrolizumab, initially in combination with bevacizumab and later as monotherapy, resulted in significant tumor shrinkage, especially in the pulmonary lesions, within the first three months. Subsequent imaging reported complete remission within 15 months and no disease recurrence at her three-year follow-up. Our case highlights one of the very few reported cases of complete remission achieved in metastatic ASPS after treatment with ICIs. ICIs could offer hope for disease remission in advanced ASPS, a rare malignancy that has proven difficult to treat successfully in the past. More studies need to be conducted to further evaluate the efficacy and any associated predictors of successful treatment.
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  • 文章类型: Case Reports
    宫颈癌最常见的是通过血液传播到肺部,肝脏,还有骨头.然而,它很少转移到脚。只有一例宫颈癌转移至足部。此外,转移性疾病的初始成像很难与感染性或其他炎症过程区分开来,特别是在高度怀疑感染源的临床环境中。这里,我们提出了一个罕见的宫颈癌转移到跟骨伪装成骨髓炎,强调诊断成像与组织学确认的重要性。
    Cervical cancer most commonly spreads hematogenously to the lungs, liver, and bone. However, it rarely metastasizes to the foot. There is only one other case of cervical cancer with metastasis to the foot. In addition, the initial imaging of metastatic disease has difficulty in differentiating from infectious or other inflammatory processes, particularly in a clinical setting highly suspicious of infectious sources. Here, we present a rare case of cervical cancer metastasizing to the calcaneus masquerading as osteomyelitis, highlighting the importance of diagnostic imaging in conjunction with histological confirmation.
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  • 文章类型: Journal Article
    最近已记录了在晚期癌症的免疫检查点抑制剂(ICI)治疗中使用抗生素和质子泵抑制剂(PPI)的预后影响。然而,目前尚不清楚这些药物如何影响晚期肾细胞癌(RCC)一线ICI联合治疗的结局.
    我们回顾性评估了128例接受一线ICI联合治疗的RCC患者的数据。在开始ICI联合治疗前一个月,根据患者的抗生素和PPI使用史进行分组。无进展生存期(PFS),总生存期(OS),在使用和不使用抗生素或PPI治疗的患者之间,比较ICI联合治疗后的客观缓解率(ORR).
    在128名患者中,30人(23%)和44人(34%)接受了抗生素和PPI,分别。与未接受抗生素治疗的患者相比,接受抗生素治疗的患者的PFS和OS较短(中位PFS:4.9vs.16.1个月,p<0.0001;OS:20.8vs.49.0个月,p=0.0034)。多变量分析显示,在调整其他协变量后,使用抗生素是较短的PFS(风险比:2.54:p=0.0002)和OS(风险比:2.56:p=0.0067)的独立预测因子。相比之下,接受PPI的患者和未接受PPI的患者的PFS或OS均无显著差异.(PFS:p=0.828;OS:p=0.105)。
    ICI联合治疗前服用抗生素与一线ICI联合治疗晚期肾癌的结果呈负相关。因此,对于接受ICI联合治疗的潜在高危患者,需要仔细监测.
    UNASSIGNED: The prognostic impact of the administration of antibiotics and proton pump inhibitors (PPIs) in immune checkpoint inhibitor (ICI) therapy for advanced cancer has recently been documented. However, how these drugs affect the outcomes of first-line ICI combination therapy for advanced renal cell carcinoma (RCC) remains unclear.
    UNASSIGNED: We retrospectively evaluated the data of 128 patients with RCC who received first-line ICI combination therapy. The patients were grouped according to their history of antibiotics and PPIs use one month before the initiation of ICI combination therapy. Progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) after ICI combination therapy were compared between patients treated with and without antibiotics or PPIs.
    UNASSIGNED: Of the 128 patients, 30 (23%) and 44 (34%) received antibiotics and PPIs, respectively. Patients treated with antibiotics exhibited shorter PFS and OS compared to those who did not receive antibiotics (median PFS: 4.9 vs. 16.1 months, p<0.0001; OS: 20.8 vs. 49.0 months, p=0.0034). Multivariate analyses showed that antibiotic administration was an independent predictor of shorter PFS (hazard ratio: 2.54: p=0.0002) and OS (hazard ratio: 2.56: p=0.0067) after adjusting for other covariates. In contrast, there were no significant differences in either PFS or OS between patients who received PPIs and those who did not. (PFS: p=0.828; OS: p=0.105).
    UNASSIGNED: Antibiotics administration before ICI combination therapy was negatively associated with outcomes of first-line ICI combination therapy for advanced RCC. Therefore, careful monitoring is required for potentially high-risk patients undergoing ICI combination therapy.
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  • 文章类型: Case Reports
    罕见但严重,免疫检查点抑制剂在肺癌治疗中可发生免疫相关不良事件,如肌炎和硬化性胆管炎.该病例报告强调了它们在pembrolizumab治疗后的共同发生,表明免疫检查点抑制剂治疗需要警惕和管理策略。
    免疫检查点抑制剂(ICI)用于肺癌的晚期治疗,但可导致免疫相关的不良事件。ICI相关的肌炎和胆管炎很少见,它们的组合以前没有报道过。这里,我们报告了第一例ICI相关性肌炎和硬化性胆管炎.一名IV期肺腺癌患者接受了一个周期的派姆单抗联合顺铂和培美曲塞治疗,出现了肌炎。泼尼松龙治疗改善了肌炎,但患者随后出现胆管炎。患者对泼尼松龙方案没有反应,霉酚酸酯,还有硫唑嘌呤,最终因肺癌恶化而死亡。尸检证实存在ICI相关的肌炎和硬化性胆管炎。
    UNASSIGNED: Rare but severe, immune-related adverse events such as myositis and sclerosing cholangitis can occur with immune checkpoint inhibitors in lung cancer treatment. This case report highlights their co-occurrence after pembrolizumab treatment, indicating the need for vigilance and management strategies in immune checkpoint inhibitors therapy.
    UNASSIGNED: Immune checkpoint inhibitors (ICI) are used in advanced treatment of lung cancer but can lead to immune-related adverse events. ICI-related myositis and cholangitis are rare, and their combination has not been previously reported. Here, we report the first case of ICI-related myositis and sclerosing cholangitis. A patient with stage IV lung adenocarcinoma who received one cycle of pembrolizumab with cisplatin and pemetrexed developed myositis. Treatment with prednisolone improved the myositis, but the patient subsequently developed cholangitis. The patient did not respond to a regimen of prednisolone, mycophenolate mofetil, and azathioprine, and eventually died due to worsening lung cancer. An autopsy confirmed the presence of ICI-related myositis and sclerosing cholangitis.
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  • 文章类型: Journal Article
    暂无摘要。
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  • 文章类型: Journal Article
    目的:最近尿路上皮癌的可用治疗选择数量有所增加。与膀胱癌相比,上尿路尿路上皮癌(UTUC)相对罕见。关于免疫检查点抑制剂(ICIs)对转移性UTUC的疗效的报道很少,和ICIs可能偶尔显示疗效较低,并引起严重的副作用。因此,预测治疗反应并酌情改变治疗策略非常重要。我们调查了在我们医院接受派姆单抗治疗的转移性UTUC患者治疗反应的预后因素。
    方法:对2018年1月至2023年6月接受派姆单抗治疗UTUC的患者进行分析。最初诊断时出现膀胱癌并发症的患者被排除在外。评估的主要终点是总生存期(OS)和无进展生存期(PFS)。使用在给予派姆单抗之前和之后获得的实验室值进行统计分析。癌症和炎症之间的关系很重要。因此,我们使用先前报道的尿路上皮癌的预后因素分析了这种关系.具体来说,治疗前C反应蛋白(CRP)水平,中性粒细胞与淋巴细胞比率(NLR),并检查NLR/白蛋白值。
    结果:分析47例患者。中位PFS为66天(24-107天),中位OS为164天(13-314天)。在多变量分析中,第一个周期前CRP水平<1是OS和PFS的有用因素[OS:p=0.004,风险比(HR)=3.244,95%置信区间(CI)=1.464-7.104;PFS:p=0.003,HR=2.998,95CI=1.444-6.225]。
    结论:CRP水平是UTUC患者派姆单抗治疗反应的预后因素。
    OBJECTIVE: The number of available treatment options for urothelial carcinoma has increased recently. Upper tract urothelial carcinoma (UTUC) is relatively rare compared with bladder cancer. There are few reports on the efficacy of immune checkpoint inhibitors (ICIs) for metastatic UTUC, and ICIs may occasionally show less efficacy and cause severe side effects. Therefore, it is important to predict the treatment response and change the treatment strategy as appropriate. We investigated the prognostic factors for treatment response in patients with metastatic UTUC treated with pembrolizumab at our hospital.
    METHODS: Patients who received pembrolizumab for UTUC between January 2018 and June 2023 were analyzed. Patients who presented with bladder cancer complications at initial diagnosis were excluded. The primary endpoints assessed were overall survival (OS) and progression-free survival (PFS). Statistical analyses were conducted using laboratory values obtained before and after pembrolizumab administration. The relationship between cancer and inflammation is important. Therefore, we analyzed this relationship using prognostic factors for urothelial carcinoma as previously reported. Specifically, pretreatment C-reactive protein (CRP) level, neutrophil-to-lymphocyte ratio (NLR), and NLR/albumin values were examined.
    RESULTS: Forty-seven patients were analyzed. The median PFS was 66 days (24-107 days), and the median OS was 164 days (13-314 days). A CRP level <1 before the first cycle was a useful factor in the multivariate analysis for both OS and PFS [OS: p=0.004, hazard ratio (HR)=3.244, 95% confidence interval (CI)=1.464-7.104; PFS: p=0.003, HR=2.998, 95%CI=1.444-6.225].
    CONCLUSIONS: CRP level is a prognostic factor for pembrolizumab treatment response in patients with UTUC.
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  • 文章类型: Journal Article
    免疫检查点抑制剂(ICIs)的监管批准是基于大的结果,随机临床试验,导致在此类试验中通常代表性不足的患者队列中结果数据有限.这项研究的目的是评估ICIs在这些独特的患者队列中的疗效和安全性。这是一个多中心,回顾性分析2011年1月1日至2018年4月1日美国6家学术和社区诊所的真实世界数据.如果患者接受了至少一个周期的ICI治疗,则将其包括在内。独特的患者队列包括年龄>75岁,非白人种族,吸烟史阳性,ECOG性能状态(PS)≥2,BMI≥30kg/m2,自身免疫性疾病(AIDs),慢性病毒感染(CVI),广泛的先验疗法(LOT),或>三个转移部位。免疫相关不良事件(irAE),总生存期(OS),在整个队列和接受PD-(L)1单药治疗的NSCLC患者中评估治疗失败的时间。在单变量分析和多变量分析中,将结果及其与独特患者队列的关联与整个NSCLCPD-(L)1单一疗法队列中没有特定特征的那些进行了比较。总的来说,1453例患者包括:56.5%-吸烟者,30.4%-非白人,22.8%-老年人,20.8%-ECOGPS≥2,15.7%-艾滋病病史,4.7%-CVI历史。常见的ICIs是nivolumab(37.1%)和pembrolizumab(22.2%)。黑人患者,与白人患者相比,经历了较少的IRAE(OR0.54,p<0.001)。ECOGPS≥2(HR=2.01,p<0.001)和以前的LOT数量增加与不良OS相关(中位OS为26.2vs.16.2vs.一个vs.9.6个月两个vs.三个先前的房子,p<0.001)。上述结果在抗PD-(L)1单一疗法非小细胞肺癌患者(n=384)中得到证实。总的来说,在这些通常代表性不足的患者队列中,ICI是安全有效的。我们注意到ECOGPS≥2和先前LOT增加与ICI疗效差相关,黑人患者,与白人患者相比,经历了较少的IrAE。
    Regulatory approval of immune checkpoint inhibitors (ICIs) was based on results of large, randomized clinical trials, resulting in limited outcomes data in patient cohorts typically underrepresented in such trials. The objective of this study was to evaluate the efficacy and safety of ICIs in these unique patient cohorts. This is a multicenter, retrospective analysis of real-world data at six academic and community clinics in the United States from 1 January 2011 to 1 April 2018. Patients were included if they had received at least one cycle of ICI treatment. Unique patient cohorts included age > 75 years, non-White race, positive smoking history, ECOG performance status (PS) ≥ 2, BMI ≥ 30 kg/m2, autoimmune diseases (AIDs), chronic viral infections (CVI), extensive prior lines of therapy (LOTs), or >three metastatic sites. Immune-related adverse events (irAEs), overall survival (OS), and time to treatment failure were evaluated in the entire cohort and in NSCLC patients treated with PD-(L)1 monotherapy. Outcomes and their association with unique patient cohorts were compared on univariate analysis and multivariate analysis to those without a particular characteristic in the entire NSCLC PD-(L)1 monotherapy cohorts. In total, 1453 patients were included: 56.5%-smokers, 30.4%-non-White, 22.8%-elderly, 20.8%-ECOG PS ≥ 2, 15.7%-history of AIDs, and 4.7%-history of CVI. The common ICIs were nivolumab (37.1%) and pembrolizumab (22.2%). Black patients, compared to White patients, experienced fewer irAEs (OR 0.54, p < 0.001). An ECOG PS of ≥2 (HR = 2.01, p < 0.001) and an increased number of previous LOTs were associated with poor OS (the median OS of 26.2 vs. 16.2 vs. 9.6 months for one vs. two vs. three prior LOTs, p < 0.001). The above results were confirmed in anti-PD-(L)1 monotherapy non-small cell lung cancer patients (n = 384). Overall, ICIs were safe and efficacious in these typically underrepresented patient cohorts. We noted ECOG PS ≥ 2 and an increased prior LOTs were associated with poor ICI efficacy, and Black patients, compared to White patients, experienced fewer irAEs.
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  • 文章类型: Journal Article
    最近,对于晚期胃癌或胃食管结合部腺癌(GC/GEJC)患者,帕博利珠单抗联合化疗的治疗方案被认为是一种有希望的治疗方案.然而,pembrolizumab联合化疗的疗效和副作用仍然缺乏循证医学证据支持.因此,进行了荟萃分析以评估该热点问题.通过搜索PubMed,EMBASE,科克伦图书馆,WebofScience,在符合纳入标准的晚期GC/GEJC患者中,pembrolizumab联合化疗与化疗的随机临床研究均被纳入.对文献质量进行评价并提取数据。还使用相关软件对数据进行分析并得出结论。在筛选14015项研究后,4项研究符合荟萃分析的条件.与单纯化疗组比较,总生存期(OS)明显延长.在程序性细胞死亡配体1(PD-L1)联合阳性评分(CPS)≥1亚组和PD-L1CPS≥10亚组分析中,结果显示,与单纯化疗组相比,pembrolizumab联合化疗组的缓解率(RR)和完全缓解率(CR)均较高.CR没有显著差异,治疗相关的不良事件,两组之间死于药物相关事件和免疫介导事件。然而,效果事件,如治疗相关的不良事件导致停药,3~5例治疗相关不良事件以及免疫介导的不良事件和输注反应在帕博利珠单抗联合化疗组中更为常见.总之,目前的荟萃分析显示,在处理高级GC/GEJC时,pembrolizumab联合化疗比单独化疗提高了治疗效果,明显更长的OS证明了这一点。此外,PD-L1CPS≥1个亚组和PD-L1CPS≥10个亚组的患者由于RR和CR较高,似乎可从派博利珠单抗联合化疗治疗中获益.然而,副作用,如导致停药的治疗相关不良事件,3-5个治疗相关的不良事件,免疫介导的不良事件和输液反应值得更多关注。
    Recently, the treatment plan of pembrolizumab plus chemotherapy was regarded as a promising treatment for patients with advanced gastric cancer or gastroesophageal junction adenocarcinoma (GC/GEJC). However, the efficacy and side effects of pembrolizumab plus chemotherapy still lack evidence-based medical evidence to support. Therefore, a meta-analysis was conducted to evaluate the hot issue. By searching PubMed, EMBASE, Cochrane Library, Web of Science, any randomized clinical studies of pembrolizumab plus chemotherapy versus chemotherapy in patients with advanced GC/GEJC met the inclusion criteria were included. The quality of the literature was evaluated and the data was extracted. A correlative software was also used to analyze the data and to draw a conclusion. After screening 14,015 studies, four studies were eligible for the meta-analysis. Compared with chemotherapy alone group, the overall survival (OS) rate was significantly longer. In programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥1 subgroup and PD-L1 CPS ≥10 subgroup analyses, the results showed that the response rate (RR) and complete response rate (CR) were both higher in pembrolizumab plus chemotherapy group compared with chemotherapy alone group. There were not significant differences in the CR, the treatment-related adverse events, succumbed to drug-related events and succumbed to immune-mediated events between the two groups. However, the effect events such as the treatment-related adverse events led to discontinuation, the 3-5 treatment-related adverse events and the immune-mediated adverse events and infusion reactions were more common in pembrolizumab plus chemotherapy group. In conclusion, the current meta-analysis revealed that, in treating advanced GC/GEJC, pembrolizumab plus chemotherapy had improved therapeutic efficacies than chemotherapy alone, as evidenced by the significantly longer OS. Furthermore, the patients in PD-L1 CPS ≥1 subgroup and PD-L1 CPS ≥10 subgroup appeared to benefit from pembrolizumab plus chemotherapy treatment because of higher RR and CR. However, side effects such as the treatment-related adverse events leading to discontinuation, the 3-5 treatment-related adverse events, and immune-mediated adverse events and infusion reactions deserved more attention.
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  • 文章类型: Journal Article
    由于全球流行率很高,发病率和相关死亡率,头颈癌,特别是口腔癌,仍然是研究和试验的主要领域。利用患者自身免疫系统来治疗口腔癌的免疫调节疗法似乎很有希望。这篇综述的目的是评估免疫治疗作为口腔癌治疗第四领域的潜力。在MEDLINE和GoogleScholar数据库中使用合适的搜索词搜索文章,包括临床试验,荟萃分析,以及在同行评审期刊上发表的人类/动物/细胞系研究。本综述共包括97篇文章。文献已经尝试了不同类型的免疫疗法,但确定基于基因组的靶向剂的精确生物标志物并找到参数以选择可能受益于免疫疗法的患者至关重要。还需要进一步的研究来估计肿瘤突变负荷和突变特征的预测价值,以便帮助口腔癌治疗反应的个性化预测。
    Owing to high global prevalence, incidence and associated mortality, cancer of head and neck particularly oral cancer remains a cardinal domain for research and trials. Immune-modulatory therapies that employ patients own immune system for therapeutic benefits in oral cancer seems promising. The aim of this review is to gauge the potential of immunotherapy as fourth domain of Oral cancer therapeutics. Articles were searched using suitable search terms in MEDLINE and Google Scholar database to include clinical trials, meta-analyses, and research in humans/animals/cell lines published in peer reviewed journals. A total of 97 articles were included in this review. Literature has several studies and trials where different types of immunotherapies has been attempted but it is crucial to identify precise biomarkers of genome based targeted agents and to find parameters to select patients who might benefit from immunotherapy. Also further research is required to estimate predictive value of tumor mutational burden and mutational signatures so as to aid in personalized prediction of oral cancer therapeutic response.
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  • 文章类型: Case Reports
    免疫检查点抑制剂(ICI)是一类经常用于癌症治疗的免疫治疗剂。可以看到的一种罕见但危及生命的并发症是ICI引起的心肌炎。我们讨论了一例pembrolizumab引起的心肌炎以及及时诊断和治疗所涉及的细微差别。一名64岁女性,既往病史对转移性右侧结直肠腺癌具有重要意义,正在接受pembrolizumab免疫治疗,呼吸急促恶化,被发现缺氧。最初的实验室分析是显着的肌钙蛋白0.35ng/mL,后来达到峰值6.01ng/mL。心电图显示房前间隔导联非特异性ST段改变,随后的超声心动图显示左心室收缩功能严重降低,射血分数为25%。冠状动脉造影显示非阻塞性冠状动脉。由于患者正在接受pembrolizumab治疗癌症,人们高度怀疑ICI诱发的心肌炎,患者开始使用类固醇进行经验性治疗。随后,做了心脏磁共振成像,证实了心肌炎的诊断.Pembrolizumab治疗停止,她开始接受指南指导的心力衰竭药物治疗。虽然ICI已经改变了癌症治疗,医疗保健提供者必须对心肌炎等免疫相关不良事件保持警惕.早期识别,管理迅速,密切监测对于优化患者预后至关重要。
    Immune checkpoint inhibitors (ICIs) are a class of immunotherapy agents that are often used in cancer treatment. A rare but life-threatening complication that can be seen is ICI-induced myocarditis. We discuss a case of pembrolizumab-induced myocarditis and the nuances involved in timely diagnosis and treatment. A 64-year-old female with a past medical history significant for metastatic right-sided colorectal adenocarcinoma undergoing immunotherapy with pembrolizumab presented with worsening shortness of breath and was found to be hypoxic. Initial laboratory analysis was remarkable for troponin of 0.35 ng/mL, which later peaked at 6.01 ng/mL. The electrocardiogram showed non-specific ST segment changes in the anteroseptal leads, and a subsequent echocardiogram revealed severely reduced left ventricular systolic function with an ejection fraction of 25%. Coronary angiography showed non-obstructive coronary arteries. As the patient was on pembrolizumab immunotherapy for cancer, there was high suspicion of ICI-induced myocarditis, and the patient was started empirically on steroids. Subsequently, cardiac magnetic resonance imaging was done, which confirmed the diagnosis of myocarditis. Pembrolizumab therapy was discontinued, and she was started on guideline-directed medical therapy for heart failure. While ICIs have transformed cancer therapy, healthcare providers must be vigilant for immune-related adverse events such as myocarditis. Early recognition, prompt management, and close monitoring are crucial for optimizing patient outcomes.
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