brentuximab vedotin

Brentuximab vedotin
  • 文章类型: Journal Article
    ECHELON-1试验证明了本妥昔单抗维多丁(BV)与多柔比星联合使用的有效性,长春碱,和达卡巴嗪作为经典霍奇金淋巴瘤的一线治疗方案。然而,周围神经病变(PN)在该方案中很常见,发生在三分之二的患者中。虽然标准处方信息建议在2级PN开始时修改BV剂量,PN的管理策略没有明确定义。最常见的是,临床医生剂量减少或停止BV,长春碱,或者两者兼而有之。我们回顾了治疗周围神经病变的循证和实用方法,强调早期检测和剂量调整。
    The ECHELON-1 trial demonstrated the effectiveness of brentuximab vedotin (BV) in combination with doxorubicin, vinblastine, and dacarbazine as a frontline treatment regimen in classical Hodgkin lymphoma. However, peripheral neuropathy (PN) is common with this regimen, occurring in up to two-thirds of patients. While standard prescribing information recommends BV dose modification at the onset of grade 2 PN, management strategies for PN are not well-defined. Most commonly, clinicians dose reduce or discontinue BV, vinblastine, or both. We review evidence-based and practical approaches for managing peripheral neuropathy, emphasizing early detection and dose modification.
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  • 文章类型: Case Reports
    该病例报告描述了一名16岁的难治性霍奇金淋巴瘤患者,该患者因Brenduximabvedotin(BV)的不良反应而发展为双侧前葡萄膜炎和中间葡萄膜炎。这是一个罕见的可能与BV相关的眼部不良反应,有视力模糊等症状,视力下降,畏光,和发红。潜在机制包括靶向葡萄膜组织中的CD30+T细胞的BV或由BV内的微管破坏剂MMAE触发的免疫应答。这突出表明需要警惕监测BV治疗患者的眼部不良事件,并进一步研究其机制和管理。
    This case report describes a 16-year-old patient with refractory Hodgkin\'s lymphoma who developed bilateral anterior and intermediate uveitis as an adverse reaction to Brentuximab vedotin (BV). This is a rare case of an ocular adverse reaction potentially related to BV, with symptoms like blurred vision, decreased visual acuity, photophobia, and redness. Potential mechanisms include BV targeting CD30+ T cells in the uveal tissue or an immune response triggered by the microtubule-disrupting agent MMAE within BV. This highlights the need for vigilant monitoring of ocular adverse events in BV-treated patients and further research into their mechanisms and management.
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  • 文章类型: Journal Article
    接受ABVD治疗的晚期霍奇金淋巴瘤患者,中期FDG-PET(iPET)阳性的患者预后不良。已显示升级至BEACOPP可改善无进展生存期(PFS)。然而,目前还缺乏随机试验来确定最佳的强化策略.我们报告了15例iPET阳性患者在ABVD后的A-AVD升级治疗结果。总体反应和完全缓解率分别为80%和60%,分别。四名患者接受了抢救治疗,然后进行了自体干细胞移植。在中位17个月的随访中,所有的病人都活着,87%完全缓解,1年PFS为57.8%。对于因年龄原因不符合BEACOPP标准的患者,合并症,或偏好,A-AVD升级可能是一个可行的替代方案。
    Patients with advanced-stage Hodgkin lymphoma treated with ABVD who have a positive interim FDG-PET (iPET) have a poor prognosis. Escalation to BEACOPP has been shown to improve progression-free survival (PFS). However, randomized trials are lacking to determine the best strategy for intensification. We report on A-AVD escalation treatment outcomes for 15 iPET-positive patients post-ABVD. Overall response and complete response rates were 80% and 60%, respectively. Four patients underwent salvage therapy followed by autologous stem cell transplantation. At a median 17-month follow-up, all patients are alive, 87% in complete remission, and 1-year PFS was 57.8%. For patients ineligible for BEACOPP due to age, comorbidities, or preference, A-AVD escalation may be a viable alternative.
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  • 文章类型: English Abstract
    背景:霍奇金淋巴瘤是一种B细胞肿瘤,预后良好,但在难治性或复发性病例中对化疗的反应较差。Brentuximab-vedotin是一种被批准用于这些病例的抗CD30单克隆抗体。这项研究旨在描述通过扩展的通路方式接受本妥昔单抗-维多汀治疗的患者的临床经验。
    方法:回顾性研究2015-2021年康塞普西翁地区医院诊断为难治性或复发性霍奇金淋巴瘤患者的临床资料。
    结果:确定了7例患者,5/7男性,年龄中位数为35岁(21-50岁)。5例混合细胞,两个是结节性硬化症。四个人在第二阶段,第三阶段的1/7,和第四阶段的3/7。先前治疗线的中位数为4(3-5),2例移植后复发。在6/7的情况下,Brentuximab-vedotin用作诱导,在一个案例中,它被用作自体骨髓移植后的维持。通过外周途径门诊给药,中位剂量为150mg,共10个周期。在一个案例中,由于毒性,需要调整剂量.6例患者中有3例完全缓解,并接受了自体干细胞移植。
    结论:本妥昔单抗-维多汀是一种低毒性的门诊药物,可以优化复发难治性霍奇金淋巴瘤患者的治疗。
    BACKGROUND: Hodgkin\'s lymphoma is a B-cell neoplasm with a good prognosis but a poor response to chemotherapy in refractory or relapsed cases. Brentuximab-vedotin is an anti-CD30 monoclonal antibody approved for use in these cases. This study aims to describe the clinical experience of patients treated with brentuximab-vedotin through expanded access modality.
    METHODS: A retrospective study on clinical information of patients diagnosed with refractory or relapsed Hodgkin\'s lymphoma treated with brentuximab-vedotin at the Regional Hospital of Concepción in the period 2015-2021.
    RESULTS: 7 patients were identified, 5/7 male, with a median age of 35 years (21-50). Five cases were mixed cellularity, and two were nodular sclerosis. Four were in stage II, 1/7 in stage III, and 3/7 in stage IV. The median number of previous treatment lines was 4 (3-5), and the relapse was post-transplantation in two cases. In 6/7 cases, brentuximab-vedotin was used as induction, and in one case, it was used as post-autologous bone marrow transplant maintenance. The administration was outpatient via a peripheral route with a median dose of 150 mg and ten cycles. In one case, dose adjustment was required due to toxicity. Three out of 6 patients achieved complete remission and underwent autologous stem cell transplantation.
    CONCLUSIONS: brentuximab-vedotin is an outpatient medication with low toxicity that can optimize the treatment of patients with relapsed-refractory Hodgkin\'s lymphoma.
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  • 文章类型: Journal Article
    背景:需要进一步研究CD30在肥大细胞上的亚细胞分布和皮肤肥大细胞增多症中嗜酸性粒细胞的存在,尤其是CD30的细胞表面表达对于全身性肥大细胞增多症对本妥昔单抗vedotin的治疗反应至关重要.
    目的:对143例皮肤肥大细胞增多症患者的147个活检标本进行肥大细胞密度和分布的调查,CD30表达频率,CD30染色模式,以及嗜酸性粒细胞的存在和分布。与临床模式的相关性。
    方法:回顾性多中心免疫组织化学研究CD30表达,皮肤肥大细胞增多症的嗜酸性粒细胞和基本临床资料。
    结果:在所有样本中均发现CD30表达(截止值:≥1%),由此在99%的样品中染色主要是细胞质的。在62%的样品中检测到额外的膜染色。CD30的表面表达在肥大细胞负荷较高的活检标本和CD30表达率较高的活检标本中更为常见。在58%的样品中混合了嗜酸性粒细胞。女性和老年患者显示出肥大细胞负荷降低的趋势。
    结论:对福尔马林固定和石蜡包埋组织进行回顾性研究,没有进行功能分析。
    结论:大多数皮肤肥大细胞增多症病例显示CD30表达的细胞表面表达,因此,原则上,可以使用抗CD30抗体进行治疗,前提是患者的总体情况需要保证。
    BACKGROUND: The subcellular distribution of CD30 on mast cells and the presence of eosinophils in cutaneous mastocytosis require further investigation, especially as the cell surface expression of CD30 is critical for the therapeutic response of systemic mastocytosis to brentuximab vedotin.
    OBJECTIVE: Investigation of 147 biopsy specimens from 143 patients with cutaneous mastocytosis for mast cell density and distribution, frequency of CD30 expression, CD30 staining patterns, and presence and distribution of eosinophils. Correlation with clinical patterns.
    METHODS: Retrospective multicenter immunohistochemical study of CD30 expression, eosinophils and basic clinical data in cutaneous mastocytosis.
    RESULTS: CD30 expression was found in all samples (cut-off: ≥1%), whereby the staining was predominantly cytoplasmic in 99% of the samples. Additional membrane staining was detected in 62% of the samples. Surface expression of CD30 was more common in biopsy specimens with a high mast cell burden and in biopsy specimens with a higher CD30 expression rate. Eosinophils were admixed in 58% of the samples. Females and older patients showed a trend of a lower mast cell burden.
    CONCLUSIONS: Retrospective study on formalin-fixed and paraffin-embedded tissue without functional analysis.
    CONCLUSIONS: Most cases of cutaneous mastocytosis show cell surface expression of CD30 expression and is, therefore, in principle, accessible for therapy with antibodies against CD30, provided the overall situation of the patient warrants.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    背景:CD30表达在间变性大细胞淋巴瘤中是普遍的,在其他一些外周T细胞淋巴瘤亚型中也有表达。将苯妥昔单抗vedotin纳入CD30阳性外周T细胞淋巴瘤患者的初始治疗可延长无进展生存期,但是还有改进的空间,特别是对于患有非间变性大细胞淋巴瘤亚型的人。
    方法:我们进行了多中心,国际,单臂,评估CHEP-BV(环磷酰胺,阿霉素,泼尼松,Brentuximabvedotin,和依托泊苷),然后在美国和加拿大的五个学术中心中,在表达CD30的外周T细胞淋巴瘤患者中进行本妥昔单抗维多汀巩固。18岁或以上新诊断的成年人,未经治疗的CD30阳性外周T细胞淋巴瘤,东部肿瘤协作组得分为0-2,并且有足够的器官功能有资格接受六个计划周期的CHEP-BV(即,第1天静脉注射1·8mg/kg本妥昔单抗vedotin,第1天静脉注射环磷酰胺750mg/m2,第1天静脉注射多柔比星50mg/m2,第1-3天每天静脉注射依托泊苷100mg/m2,并在第1-5天每天口服泼尼松100mg)与预防性G-CSF。对治疗有反应的患者可以在自体造血干细胞移植(HSCT)后或在CHEP-BV后直接接受本妥昔单抗维多汀巩固多达十个周期。主要终点是接受研究治疗并完成安全性评估期(以确认CHEP-BV中本妥昔单抗vedotin的推荐2期剂量)的参与者的3+3安全性引入期间的不可接受的毒性,以及接受研究治疗并进行反应评估的参与者的CHEP-BV诱导治疗后的完全缓解率。该研究已在ClinicalTrials.gov(NCT03113500)注册,这个队列完成了试验。该试验正在进行中,招募了一个新的队列。
    结果:54例患者被筛选为合格,48例患者被纳入研究。参与者(18[38%]女性和30[63%]男性;34[71%]白人,四个[8%]黑色,五个[10%]亚洲人,十个[21%]西班牙裔,和37[77%]非西班牙裔人)在2017年12月4日至2021年6月14日之间招募和登记,并随访至2023年8月25日,数据库被锁定进行分析。48名参与者可评估毒性,47人的反应可评估(1名参与者在反应评估前死于COVID-19).在安全导入期间,六个参与者中的一个有不可接受的毒性(即,在广泛骨髓受累的参与者中,血小板计数<10000/mm3),并证实了CHEP-BV中建议的2期剂量为1·8mg/kg本妥昔单抗vedotin。在CHEP-BV完成时,47名参与者中有37名完全回应,完全缓解率为79%(95%CI64-89)。最常见的3级或更高的CHEP-BV相关毒性是中性粒细胞减少症(48个中的14个[29%]),白细胞减少症(11[23%]),贫血(十[21%]),发热性中性粒细胞减少症(十[21%]),淋巴细胞减少(九[19%]),和血小板减少症(9[19%])。没有治疗相关的死亡。
    结论:在非间变性大细胞淋巴瘤以外的主要表达CD30的外周T细胞淋巴瘤患者中,CHEP-BV(有或没有自体HSCT),然后进行本妥昔单抗维多汀巩固是安全且活跃的。
    背景:SeaGen,白血病和淋巴瘤协会,淋巴瘤研究基金会,和美国国立卫生研究院的国家癌症研究所。
    BACKGROUND: CD30 expression is universal in anaplastic large-cell lymphoma and is expressed in some other peripheral T-cell lymphoma subtypes. Incorporation of brentuximab vedotin into initial therapy for people with CD30-positive peripheral T-cell lymphomas prolonged progression-free survival, but there is room for improvement, especially for people with non-anaplastic large-cell lymphoma subtypes.
    METHODS: We conducted a multicentre, international, single-arm, phase 2 trial to evaluate the safety and activity of CHEP-BV (cyclophosphamide, doxorubicin, prednisone, brentuximab vedotin, and etoposide) followed by brentuximab vedotin consolidation in patients with CD30-expressing peripheral T-cell lymphomas across five academic centres in the USA and Canada. Adults aged 18 years or older with newly diagnosed, untreated CD30-positive peripheral T-cell lymphomas, Eastern Cooperative Oncology Group score of 0-2, and adequate organ function were eligible to receive six planned cycles of CHEP-BV (ie, 1·8 mg/kg brentuximab vedotin intravenously on day 1, cyclophosphamide 750 mg/m2 intravenously on day 1, doxorubicin 50 mg/m2 intravenously on day 1, etoposide 100 mg/m2 daily intravenously on days 1-3, and prednisone 100 mg daily orally on days 1-5) with prophylactic G-CSF. Patients who responded to the treatment could receive brentuximab vedotin consolidation for up to ten additional cycles either after autologous haematopoietic stem-cell transplantation (HSCT) or directly after CHEP-BV. The primary endpoints were unacceptable toxicity during a 3-plus-3 safety lead-in in participants who received study treatment and completed the safety evaluation period (to confirm the recommended phase 2 dose of brentuximab vedotin in CHEP-BV) and the complete response rate after CHEP-BV induction therapy in participants who received study treatment and had response evaluation. The study was registered at ClinicalTrials.gov (NCT03113500), and this cohort completed the trial. The trial is ongoing with the enrolment of a new cohort.
    RESULTS: 54 patients were screened for eligibility and 48 were eligible for the study. The participants (18 [38%] women and 30 [63%] men; 34 [71%] White, four [8%] Black, five [10%] Asian, ten [21%] Hispanic, and 37 [77%] non-Hispanic people) were recruited and enrolled between Dec 4, 2017, and June 14, 2021, and followed up until Aug 25, 2023, when the database was locked for analysis. 48 participants were evaluable for toxicity, and 47 were evaluable for response (one participant died from COVID-19 before response assessment). During the safety lead-in, one of six participants had an unacceptable toxicity (ie, platelet count <10 000 per mm3 in a participant with extensive bone marrow involvement), and the proposed phase 2 dose of 1·8 mg/kg brentuximab vedotin in CHEP-BV was confirmed. At completion of CHEP-BV, 37 of 47 participants had complete response, yielding a complete response rate of 79% (95% CI 64-89). The most common CHEP-BV-related toxicities of grade 3 or higher were neutropenia (14 [29%] of 48), leukopenia (11 [23%]), anaemia (ten [21%]), febrile neutropenia (ten [21%]), lymphopenia (nine [19%]), and thrombocytopenia (nine [19%]). There were no treatment-related deaths.
    CONCLUSIONS: In patients with mostly CD30-expressing peripheral T-cell lymphomas other than non-anaplastic large-cell lymphoma, CHEP-BV (with or without autologous HSCT) followed by brentuximab vedotin consolidation was safe and active.
    BACKGROUND: SeaGen, Leukemia and Lymphoma Society, Lymphoma Research Foundation, and the National Cancer Institute of the National Institutes of Health.
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  • 文章类型: Journal Article
    加拿大全民医疗系统内的治疗需要成本效益分析,导致相对于美国医疗保健的延误。霍奇金淋巴瘤(HL)患者通常预后良好,但是那些在移植后复发或没有资格接受移植的人受益于新疗法,包括Brentuximabvedotin(BV)。BV于2011年获得FDA批准,但直到2014年才获得加拿大资助。为了评估访问延迟的影响,我们比较了美国批准前/后美国患者(保险公司)和加拿大患者生存率的变化.患者16-64岁,在2007-2010年(第1期)和2011-2014年(第2期)从美国SEER和加拿大癌症登记处诊断为HL。使用批准日期(替代),因为注册中心无法获得治疗。Kaplan-Meier存活曲线和调整后的Cox回归模型按保险类别比较了不同时期之间的生存率。在12,003名美国和4210名加拿大患者中,美国患者的生存率较好(校正后风险比(aHR)0.87(95CI0.77-0.98));加拿大患者的生存率改善(aHR0.84(95CI0.69-1.03)相似,但无显著性.保险公司之间的比较显示,美国无保险和医疗补助的生存率明显低于美国私人保险和加拿大患者。鉴于肿瘤资助日益复杂的性质,这值得进一步调查,以确保公平获得治疗发展。
    Cost-effectiveness analyses are required for therapies within Canada\'s universal healthcare system, leading to delays relative to U.S. healthcare. Patients with Hodgkin lymphoma (HL) generally have an excellent prognosis, but those who relapse after or are ineligible for transplant benefit from novel therapies, including brentuximab vedotin (BV). BV was FDA-approved in 2011 but not Canadian-funded until 2014. To assess the impact of access delays, we compared changes in survival for U.S. (by insurer) and Canadian patients in periods pre/post-U.S. approval. Patients were 16-64 years, diagnosed with HL in 2007-2010 (Period 1) and 2011-2014 (Period 2) from the U.S. SEER and Canadian Cancer Registries. Approval date (surrogate) was utilized as therapy was unavailable in registries. Kaplan-Meier survival curves and adjusted Cox regression models compared survival between periods by insurance category. Among 12,003 U.S. and 4210 Canadian patients, survival was better in U.S. patients (adjusted hazard ratio (aHR) 0.87 (95%CI 0.77-0.98)) between periods; improvement in Canadian patients (aHR 0.84 (95%CI 0.69-1.03) was similar but non-significant. Comparisons between insurers showed survival was significantly worse for U.S. uninsured and Medicaid vs. U.S. privately insured and Canadian patients. Given the increasingly complex nature of oncologic funding, this merits further investigation to ensure equity in access to therapy developments.
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  • 文章类型: English Abstract
    Objective: To evaluate the efficacy and safety of CD30 antibody-drug conjugates (ADC) brentuximab vedotin (BV) combined with chemotherapy in children with refractory or relapsed classic Hodgkin\'s lymphoma (R/R cHL). Methods: Clinical data (including age, gender, B symptoms, clinical stage, previous treatment, etc.) of the 10 R/R cHL children diagnosed and treated at Beijing Children\'s Hospital Affiliated to Capital Medical University from October 2021 to August 2023 were analyzed retrospectively. According to the different intensity of chemotherapy drugs, the dose of BV applied in the same course of treatment was 1.8 mg/kg for BV applied once every 3 weeks, and 1.2 mg/kg for BV applied once every 2 weeks. All 10 patients received at least 2 cycles of BV combined with chemotherapy and were evaluated every 2 cycles. The patients were followed up until May 31, 2024. The infusion reactions and adverse reactions after treatment were recorded. Results: In all 10 patients, there were 7 males and 3 females, the age ranged from 5.3-16.9 years, and there were 6 cases of refractory and 4 cases of relapsed. There were 6 cases of nodular sclerosis type, 2 cases of mixed cell type, 1 case of lymphocyte-rich type, and 1 case of lymphodepletion type. There were 5 cases of stage Ⅳ and 5 cases of stage Ⅲ. Previous treatment was mainly chemotherapy, 4 cases received radiotherapy and 1 case received programmed cell death protein 1 (PD-1) antibody therapy. The follow-up time ranged from 9 to 27 months. A total of 43 courses with 49 doses of BV alone or combined with chemotherapy were recorded, and the number of courses was 2 to 10 times. All 10 children responded to the treatment, and 9 achieved complete remission. BV infusion was successfully completed in all cases. A total of 28 cases of grade 3 or above adverse events were recorded, mainly myelosuppression, all of which were related to chemotherapy and did not affect sequential treatment. Conclusion: Brentuximab vedotin has demonstrated efficacy and a tolerable safety profile in the treatment of refractory and relapsed CD30-positive Hodgkin\'s lymphoma in children.
    目的: 评估CD30抗体-药物偶联物(ADC)维布妥昔单抗(BV)联合化疗治疗儿童难治或复发经典性霍奇金淋巴瘤(R/R cHL)的有效性和安全性。 方法: 回顾性分析2021年10月至2023年8月在首都医科大学附属北京儿童医院诊治的10例R/R cHL患儿的临床资料(包括年龄、性别、B症状、临床分期、既往治疗情况等),10例患儿均接受至少2周期BV联合化疗,根据化疗药物强度的不同决定与其同疗程应用的BV剂量,每3周1次应用BV者剂量为1.8 mg/kg,每2周1次应用BV者剂量为1.2 mg/kg。每2个周期评估患儿缓解情况,随访至2024年5月31日。记录用药期间有无输注反应及用药后的不良反应。 结果: 10例患儿中男7例,女3例;年龄5.3~16.9岁;难治6例,复发4例;结节硬化型6例,混合细胞型2例,富于淋巴细胞型1例,淋巴细胞消减型1例。临床分期Ⅳ期5例,Ⅲ期5例。既往接受治疗以化疗为主,4例患儿曾接受放疗,1例患儿曾接受程序性死亡受体1(PD-1)抗体治疗。随访时间为9~27个月,共计43周期单独应用BV或BV联合不同方案化疗,疗程数为2~10个,10例患儿均无事件生存,9例患儿持续完全缓解。BV均顺利完成输注,共记录到28例次患儿发生3级以上的不良事件,以骨髓抑制为主,均与化疗相关,均未影响序贯治疗。 结论: BV治疗儿童难治及复发CD30阳性霍奇金淋巴瘤的早期显效,安全性可耐受。.
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