PD-1 inhibitor

PD - 1 抑制剂
  • 文章类型: Journal Article
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  • 文章类型: Case Reports
    上皮样血管内皮瘤是一种罕见的血管恶性肿瘤,目前,这种疾病没有标准的治疗方案,现有的治疗方案疗效有限。在这个案例报告中,我们介绍了1例前列腺上皮样血管内皮瘤的肺和淋巴结转移患者,该患者获得了明显的部分缓解。这是通过尼武单抗与伊匹单抗和脂质体多柔比星交替治疗来实现的,到目前为止,无进展生存期超过6个月。治疗自始至终耐受性良好。我们的报告表明,与抗PD-1抗体加阿霉素交替的双重免疫疗法可能是上皮样血管内皮瘤的潜在治疗方式。然而,需要更多的样本研究来确定该治疗策略的有效性,并且必须继续监测该患者以维持无进展生存期和总生存期.
    Epithelioid hemangioendothelioma is a rare vascular malignancy, and currently, there is no standard treatment regimen for this disease and existing treatment options have limited efficacy. In this case report, we present a patient with lung and lymph node metastases from prostate epithelioid hemangioendothelioma who achieved a significant partial response. This was accomplished through alternating nivolumab therapy with ipilimumab and liposomal doxorubicin, resulting in a progression-free-survival more than 6 months to date. The treatment was well-tolerated throughout. Our report suggests that dual immunotherapy alternating with anti-PD-1antibody plus doxorubicin may be a potential treatment modality for epithelioid hemangioendothelioma. However, larger sample studies are necessary to ascertain the effectiveness of this treatment strategy and it is essential to continue monitoring this patient to sustain progression-free survival and overall survival.
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  • 文章类型: Journal Article
    该研究旨在分析PD-1抑制剂加或不含内皮抑素的化疗对IV期肺鳞癌(LUSC)的疗效和安全性。
    共纳入219例IV期LUSC患者。120例接受PD-1抑制剂加化疗,有或没有内皮抑素(IC±A),其中39人接受了内皮抑素(IC+A),81人没有接受内皮抑素(IC-A).99例接受有或没有内皮抑素的化疗(C±A)。终点包括总生存期(OS),无进展生存期(PFS),不良事件(AE),和免疫相关不良事件(irAE)。
    IC±A组与C±A组的中位PFS分别为8个月和4个月(P<0.001),中位OS分别为17个月和9个月(P<0.001)。IC±A组和C±A组任何级别的不良事件发生率差异均无统计学意义(P>0.05)。IC+A组与IC-A组的中位PFS分别为11个月和7个月(P=0.024),中位OS分别为34个月和15个月(P=0.01)。IC+A组与IC-A组之间的所有分级AE和irAE均无显著差异(P>0.05)。亚组分析显示,LIPI=0的患者在IC+A组具有显著的OS和PFS获益,而对于LIPI=1-2的患者,IC+A组和IC-A组的OS和PFS获益无显著差异.
    PD-1抑制剂联合内皮抑素化疗可能是IV期LUSC患者的一线治疗。
    UNASSIGNED: The study aimed to analyze the efficacy and safety of PD-1 inhibitors plus chemotherapy with or without endostatin for stage IV lung squamous cell carcinoma (LUSC).
    UNASSIGNED: A total of 219 patients with stage IV LUSC were included. 120 received PD-1 inhibitors plus chemotherapy with or without endostatin (IC ± A), of which 39 received endostatin (IC+A) and 81 did not receive endostatin (IC-A). 99 received chemotherapy with or without endostatin (C ± A). Endpoints included overall survival (OS), progression-free survival (PFS), adverse events (AEs), and immune-related adverse events (irAEs).
    UNASSIGNED: The median PFS in the IC ± A group versus the C ± A group was 8 and 4 months (P < 0.001), and the median OS was 17 and 9 months (P < 0.001). There was no significant difference in any grade AEs between the IC ± A and C ± A groups (P > 0.05). The median PFS in the IC+A group versus the IC-A group was 11 and 7 months (P = 0.024), and the median OS was 34 and 15 months (P = 0.01). There was no significant difference between the IC+A group and the IC-A group for all grade AEs and irAEs (P > 0.05). The subgroup analysis showed that patients with LIPI = 0 had significant OS and PFS benefits in IC+A group, while for patients with LIPI = 1-2, there was no significant difference in OS and PFS benefits between the IC+A group and IC-A group.
    UNASSIGNED: PD-1 inhibitors plus chemotherapy with endostatin might be first-line treatment for patients with stage IV LUSC.
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  • 文章类型: Journal Article
    对寡转移以外的肝细胞癌(HCC)的策略治疗是有限的。晚期HCC的全身治疗的最佳顺序尚不清楚。我们的研究旨在评估乐伐替尼联合PD-1抑制剂对晚期HCC的疗效。
    我们的回顾性研究共纳入了232例患者。患者分为三组。(a)Lenvatinib加同时PD-1抑制剂(同时组,n=58);(b)患者在肿瘤进展前接受PD-1抑制剂,并继续lenvatinib给药(PD组之前,n=77);(c)患者在肿瘤进展后接受PD-1抑制剂(PD组,n=97)。分析3组患者的总生存期(OS)和无进展生存期(PFS)。
    估计的6-,12-,同期组患者的18-和24-monOS为100%,93.1%,63.4%,48.3%,而OS率为100%,78%,36.3%,PD组之前的23.6%,99%,61.2%,22.1%,术后PD组为7.5%。3组同时使用PD-1抑制剂后,OS率均明显提高(P<0.001)。估计的3,6-,患者9个月和12个月的PFS率为89.6%,44.8%,24.6%,6%在后PD组,90.9%,59.7%,27.3%,PD前组12.4%,98.3%,81%,51.7%,同时组39.7%,分别。三组间PFS差异有统计学意义(P<0.001)。
    乐伐替尼和PD-1抑制剂的同步给药显著提高了生存率。同步组合可以代表肝癌中超越寡转移的有希望的策略。
    UNASSIGNED: Strategies therapy for hepatocellular carcinoma (HCC) beyond oligometastasis are limited. The optimal sequence of systemic treatment for advanced HCC is not yet clear. Our study aims to evaluate the effectiveness of simultaneous lenvatinib combined PD-1 inhibitor on advanced HCC beyond oligometastasis.
    UNASSIGNED: A total of 232 patients were enrolled in our retrospective study. Patients divided into three groups. (a) Lenvatinib plus simultaneous PD-1 inhibitor (Simultaneous group, n=58); (b) patients received PD-1 inhibitor before the tumor progression with continued lenvatinib administration (Before PD group, n=77); (c) patients received PD-1 inhibitor after the tumor progression (After PD group, n=97). To analyze overall survival (OS) and progression-free survival (PFS) among the three groups.
    UNASSIGNED: The estimated 6-, 12-, 18- and 24-mon OS for Simultaneous group patients were 100%, 93.1%, 63.4%, 48.3%, whereas the OS rates were 100%, 78%, 36.3%, 23.6% in Before PD group, and 99%, 61.2%, 22.1%, 7.5% in After PD group. The OS rates were obviously improved with the use of simultaneous PD-1 inhibitor among the three groups (P <0.001). The estimated 3-, 6-, 9- and 12-month PFS rates for patients were 89.6%, 44.8%, 24.6%, 6% in After PD group, 90.9%, 59.7%, 27.3%, 12.4% in Before PD group and 98.3%, 81%, 51.7%, 39.7% in Simultaneous group, respectively. PFS rate was significantly different among the three groups (P <0.001).
    UNASSIGNED: Synchronous administration of lenvatinib and PD-1 inhibitors improved survival rate significantly. The synchronous combination could represent a promising strategy in HCC beyond oligometastasis.
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  • 文章类型: Journal Article
    目的:高危人群的预后,局部晚期宫颈癌(LACC)在同步放化疗(CCRT)后仍然较差.我们研究了程序性细胞死亡蛋白1(PD-1)抑制剂是否可以增强CCRT的作用。方法:回顾性队列研究比较CCRT组(n=82)和PD-1抑制剂加CCRT组(n=70)的疗效和安全性。结果:与CCRT组相比,PD-1抑制剂加CCRT组的客观缓解率明显更高,中位无进展生存期,白细胞减少和疲劳。在CCRT中添加PD-1抑制剂显示出总体生存的有利趋势,但无统计学意义。结论:PD-1抑制剂联合CCRT在高危LACC中具有显著的生存获益和可控制的安全性。
    [方框:见正文]。
    Aim: The prognosis of high-risk, locally advanced cervical cancer (LACC) remains poor following concurrent chemoradiotherapy (CCRT). We investigated whether the effect of CCRT can be enhanced by programmed cell death protein 1 (PD-1) inhibitor. Methods: A retrospective cohort study was conducted to compare the efficacy and safety of CCRT group (n = 82) and PD-1 inhibitor plus CCRT group (n = 70). Results: Compared with the CCRT group, the PD-1 inhibitor plus CCRT group had significantly higher objective response rate, median progression-free survival, leukopenia and fatigue. The addition of PD-1 inhibitor to CCRT showed a favorable trend in overall survival without statistical significance. Conclusion: PD-1 inhibitor plus CCRT presented a significant survival benefit and a manageable safety profile in high-risk LACC.
    [Box: see text].
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  • 文章类型: Case Reports
    PD-1抑制剂在治疗不可切除/转移性驱动基因阴性NSCLC方面表现出疗效,尽管存在潜在的免疫相关不良事件(irAEs)。其中,免疫检查点抑制剂相关性心肌炎(ICI-M)罕见但致命.这项研究提出了ICI-M在肺癌患者中的最初成功实例,在治疗期间,低剂量糖皮质激素在恶化后挽救。
    一名78岁男性,有IV期pT3N2M1非小细胞肺癌病史,接受了四个周期的姑息性化疗,导致稳定的疾病(SD)。在进一步化疗下降之后,患者过渡至靶向治疗方案,包括安洛替尼联合PD-1抑制剂免疫疗法.PD-1抑制剂给药后第26天,患者表现为2级免疫介导性心肌炎。开始接受1mg/kg甲基强的松龙联合免疫球蛋白休克治疗3天,实现对症控制。尽管如此,当甲基强的松龙剂量逐渐减少至4-8mg/3-4d时,病情恶化,需要转移到重症监护室。甲基强的松龙剂量增加至80mg/天,持续3天,随后每周逐渐减少三分之一到三分之二,最终导致病人安全出院。
    与检查点抑制剂相关的免疫相关性心肌炎通常通过大剂量糖皮质激素治疗得到有效控制。然而,在亚洲人口中,低剂量糖皮质激素越来越多地用于抢救治疗,与欧洲人群相比,产生有利的结果并改善预后。
    UNASSIGNED: PD-1 inhibitors exhibit efficacy in managing unresectable/metastatic driver gene-negative NSCLC, albeit with potential immune-related adverse events (irAEs). Among these, immune checkpoint inhibitor-associated myocarditis (ICI-M) is rare yet lethal. This study presents the initial successful instance of ICI-M in a lung cancer patient, rescued by low-dose glucocorticoids post-deterioration during treatment.
    UNASSIGNED: A 78-year-old male with a medical history of stage IV pT3N2M1 NSCLC underwent four cycles of palliative chemotherapy, resulting in stable disease (SD). Subsequent to declining further chemotherapy, the patient was transitioned to a targeted therapy regimen comprising Anlotinib in conjunction with PD-1 inhibitor immunotherapy. On the 26th day post-administration of the PD-1 inhibitor, the patient manifested Grade 2 immune-mediated myocarditis. Treatment encompassing 1mg/kg methylprednisolone combined with immunoglobulin shock therapy was initiated for 3 days, achieving symptomatic control. Nonetheless, upon tapering methylprednisolone dosage to 4-8mg/3-4d, the condition deteriorated, necessitating transfer to the intensive care unit. Methylprednisolone dosage was escalated to 80mg/day for 3 days, followed by gradual reduction by one-third to two-thirds weekly, culminating in the patient\'s safe discharge from the hospital.
    UNASSIGNED: Immune-related myocarditis linked to checkpoint inhibitors is often managed effectively with high-dose glucocorticoid therapy. However, in Asian populations, low-dose glucocorticoids are increasingly utilized for salvage therapy, yielding favorable outcomes and improving prognosis compared to European populations.
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  • 文章类型: Journal Article
    目的:Retifanlimab是针对程序性死亡1的人源化免疫球蛋白G4单克隆抗体,正在几种实体瘤类型中进行研究。我们报告了在POD1UM-101扩展队列中接受retifanlimab治疗的复发性微卫星不稳定性高(MSI-H)/错配修复缺陷(dMMR)子宫内膜癌患者的最终结果。
    方法:符合条件的患者(≥18岁;组织学证实/不可切除/复发,MSI-H/dMMR子宫内膜癌;检查点抑制剂初治)每4周静脉注射retifanlimab500mg,持续≤2年。主要终点是安全性/耐受性。
    结果:在数据截止时(2023年5月17日),76名患者接受了至少一次retifanlimab剂量。中位(范围)年龄为67(49-88)岁;88.2%的患者患有复发性转移性疾病,80.3%的患者患有内脏转移。75例患者(98.7%)接受过至少一次全身治疗。retifanlimab暴露中位数为10.0(0.03-25.9)个月;23例患者完成治疗。38例患者(50.0%)有≥3级治疗紧急不良事件(TEAE),最常见的贫血(n=10[13.2%])。63例患者(82.9%)有治疗相关的AE(TRAEs;≥3级,n=14[18.4%]);最常见的是疲劳(n=14[18.4%])。两名患者有导致死亡的TEAE;没有TRAE是致命的。39例患者有客观反应(51.3%;95%CI,39.6-63.0%);19例患者(25.0%)完全缓解,20例(26.3%)部分缓解。中位无进展生存期为12.2个月;30例患者(76.9%)的反应持续时间(DOR)≥12个月。中位随访时间26.0个月后未达到中位DOR。
    结论:Retifanlimab在治疗前的复发性MSI-H/dMMR子宫内膜癌患者中通常具有良好的耐受性,并表现出令人鼓舞的抗肿瘤活性。
    OBJECTIVE: Retifanlimab is a humanized immunoglobulin G4 monoclonal antibody against programmed death 1 being investigated in several solid tumor types. We report final results from patients with recurrent microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) endometrial cancer treated with retifanlimab in a POD1UM-101 expansion cohort.
    METHODS: Eligible patients (≥18 years; histologically proven/unresectable/recurrent, MSI-H/dMMR endometrial cancer; checkpoint inhibitor naive) received retifanlimab 500 mg intravenously every 4 weeks for ≤2 years. Primary endpoint was safety/tolerability.
    RESULTS: At data cutoff (May 17, 2023), 76 patients had received at least one retifanlimab dose. Median (range) age was 67 (49-88) years; 88.2% of patients had recurrent metastatic disease and 80.3% had visceral metastases. Seventy-five patients (98.7%) had received at least one prior systemic therapy. Median retifanlimab exposure was 10.0 (0.03-25.9) months; 23 patients completed treatment. 38 patients (50.0%) had grade ≥3 treatment-emergent adverse events (TEAEs), most commonly anemia (n = 10 [13.2%]). 63 patients (82.9%) had treatment-related AEs (TRAEs; grade ≥3, n = 14 [18.4%]); most common was fatigue (n = 14 [18.4%]). Two patients had TEAEs that led to death; no TRAEs were fatal. 39 patients had objective responses (51.3%; 95% CI, 39.6-63.0%); 19 patients (25.0%) had complete response and 20 (26.3%) had partial response. Median progression-free survival was 12.2 months; 30 patients (76.9%) had duration of response (DOR) ≥12 months. Median DOR was not reached after median follow-up time of 26.0 months.
    CONCLUSIONS: Retifanlimab was generally well tolerated and demonstrated encouraging anti-tumor activity in patients with pre-treated recurrent MSI-H/dMMR endometrial cancer.
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  • 文章类型: Case Reports
    背景:免疫检查点抑制剂是癌症治疗领域中相对较新的进展。因此,它们的不利影响尚未得到充分理解,只有最近的文献记录了继发于其利用的自身免疫现象。特异性免疫检查点抑制剂最近与重症肌无力的发展有关,传统上已知在患者中自发表现。鉴于此演示文稿的相对罕见,误诊的风险以及随后的死亡率和发病率令人担忧。
    方法:我们讨论了一名73岁男性在开始使用Pembrolizumab治疗后不久出现重症肌无力和肌炎临床症状的病例。重症肌无力的诊断最初是在外部医院漏诊的,这延迟了适当治疗的开始。
    结论:虽然免疫检查点抑制剂继发的“从头”疾病的发病率可能正在增加,关于最佳治疗方案的指南尚不存在,当面对围绕新生重症肌无力患者的临床决策时,许多提供者不知所措。因此,我们的目标是强调早期识别这种疾病的重要性,并强调随着免疫检查点抑制剂的使用变得越来越普遍,需要标准的护理。
    BACKGROUND: Immune checkpoint inhibitors are a relatively new advancement in the world of cancer therapy. As such, their adverse effects have yet to be fully understood, with only recent literature documenting autoimmune phenomena secondary to their utilization. Specific immune checkpoint inhibitors have recently been linked with the development of myasthenia gravis, which is classically known to manifest spontaneously in patients. Given the relative rarity of this presentation, the risk of misdiagnosis and subsequent mortality and morbidity is concerning.
    METHODS: We discuss the case of a 73-year-old male who presented with clinical symptoms of myasthenia gravis and myositis shortly after beginning treatment with Pembrolizumab. The diagnosis of myasthenia gravis was initially missed at an outside hospital, which delayed initiation of proper treatment.
    CONCLUSIONS: While the incidence of \"de-novo\" diseases secondary to immune checkpoint inhibitors might be increasing, guidelines regarding best treatment options do not yet exist, leaving many providers at a loss when faced with making clinical decisions surrounding patients with De novo myasthenia gravis. Thus, our goal is to underscore the importance of early recognition of this disease, and emphasize the need for a standard of care as immune checkpoint inhibitors usage becomes more prevalent.
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  • 文章类型: Case Reports
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  • 文章类型: Journal Article
    Lenvatinib或索拉非尼联合程序性细胞死亡蛋白-1(PD-1)抑制剂作为晚期肝细胞癌(HCC)肝外转移(EHM)的推荐治疗。我们旨在比较Lenvatinib加PD-1抑制剂(LenPD-1)与索拉非尼加PD-1(SoraPD-1)作为EHMHCC的初始治疗的预后。
    纳入了229例EHMHCC患者的总和,Sora+PD-1组127人,Len+PD-1组102人。通过倾向得分匹配(PSM),我们比较了总生存期(OS),无进展生存期(PFS),这两组之间的患者安全。
    Sora+PD-1组和Len+PD-1组的中位OS分别为13.0个月和14.2个月。6-,12-,24个月OS率为92.9%,Sora+PD-1组的58.9%和5.6%,93.1%,Len+PD-1组分别为61.8%和22.6%,分别。Len+PD-1组的OS明显优于Sora+PD-1组(P=0.002)。3、6-,12个月的PFS率为76.4%,Sora+PD-1组分别为27.6%和1.6%,86.2%,Len+PD-1组分别为50.5%和12.2%,分别。与Sora+PD-1组相比,Len+PD-1组PFS明显优于对照组(P<0.001)。亚组内的分析表明,LenPD-1组接受TACE的患者的OS比SoraPD-1组显着(p=0.003)。
    对于EHM患者,Len+PD-1组比Sora+PD-1组具有更长的OS和PFS。此外,Len+PD-1治疗可改善接受TACE的患者的OS。对于没有TACE的患者,Sora+PD-1组和Len+PD-1组之间无显著性差异.
    UNASSIGNED: Lenvatinib or Sorafenib combined with programmed cell death protein-1 (PD-1) inhibitor as recommend treatment of advanced hepatocellular carcinoma (HCC) with extrahepatic metastasis (EHM). We aimed to compared the prognosis of Lenvatinib plus PD-1 inhibitor (Len+PD-1) versus Sorafenib plus PD-1 (Sora+PD-1) as an initial therapy for HCC with EHM.
    UNASSIGNED: Incorporating a sum of 229 HCC patients with EHM were encompassed within this study, with 127 in the Sora+PD-1 group and 102 in the Len+PD-1 group. Through propensity score matching (PSM), we compared overall survival (OS), progression-free survival (PFS), and patient safety between these two groups.
    UNASSIGNED: The median OS were 13.0 months and 14.2 months in the Sora+PD-1 group and Len+PD-1 group. The 6-, 12-, and 24-month OS rates were 92.9%, 58.9% and 5.6% in Sora+PD-1 group and 93.1%, 61.8% and 22.6% in Len+PD-1 group, respectively. The Len+PD-1 group had obviously better OS than the Sora+PD-1 group (P = 0.002). The 3-, 6-, and 12-month PFS rates were 76.4%, 27.6% and 1.6% in Sora+PD-1 group and 86.2%, 50.5% and 12.2% in Len+PD-1 group, respectively. Compared with Sora+PD-1 group, the Len+PD-1 group had obviously better PFS (P < 0.001). Analysis within subgroups showed that OS was significant in patients receiving TACE in Len+PD-1 group than Sora+PD-1 group (p = 0.003).
    UNASSIGNED: Len+PD-1 group had longer OS and PFS than Sora+PD-1 group for patient with EHM. In addition, OS in patients received TACE was improved with Len+PD-1 treatment. For patients without TACE, there was no significance between Sora+PD-1 and Len+PD-1 groups.
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