抗霍奇金淋巴瘤新药贝伦妥单抗-维多汀

贝伦妥单抗-维多汀(brentuximab vedotin)是一种以CD30为靶点的新型肿瘤靶向治疗药物。2011年8月11日获FDA批准用于治疗霍奇金淋巴瘤和系统性间变性大细胞淋巴瘤(sALCL)。本文对其药理作用、药动学、药物相互作用、临床研究和安全性进行综述。     

Brentuximab vedotin: its role in the treatment of anaplastic large cell and Hodgkin's lymphoma

Brentuximab vedotin is being developed in a joint collaboration between Seattle Genetics and Millennium: The Takeda Oncology Company. In August 2011, it was approved by the FDA for the treatment of patients with Hodgkin's lymphoma (HL) and anaplastic large cell lymphoma (ALCL). Brentuximab vedotin is an antibody-drug conjugate that specifically targets the TNF receptor superfamily member 8 (CD30) antigen on the surface of cancer cells to induce cell death. Brentuximab vedotin has shown efficacy in inducing apoptosis in HL and ALCL cell lines that express CD30 and reducing tumor size in preclinical models. Brentuximab vedotin is under clinical evaluation for the treatment of relapsed or refractory HL and ALCL in both adults and children. It is being investigated for use as a combination agent with pre-existing frontline chemotherapies and as a stand-alone salvage therapy for use prior to autologous stem cell transplant. Treatment with brentuximab vedotin is generally well tolerated although it is associated with grade 1-2 adverse reactions such as neutropenia and there have been reports of grade 3-4 serious adverse events. In particular its use with chemotherapy regimens that include bleomycin is contraindicated because of adverse pulmonary effects.     

Disitamab vedotin: a novel antibody-drug conjugates for cancer therapy

Human epidermal growth factor receptor 2 (HER2) regulates cell mitosis, proliferation, and apoptosis. Trastuzumab is a HER2-targeted monoclonal antibody (mAB), which can prolong the overall survival rate of patients with HER2 overexpression in later periods of gastric cancer and breast cancer. Although anti-HER2 monoclonal antibody has a curative effect, adjuvant chemotherapy is still necessary to upgrade the curative effect maximumly. Antibody-drug conjugate (ADC) is a kind of therapeutic drug that contains antigen-specific antibody and cytotoxic payload, which can improve the survival time of tumor patients. To date, there are several HER2-ADC products on the market, for which two anti-HER2 ADC (trastuzumab emtansine and trastuzumab deruxtecan) have been authorized by the FDA for distinct types of HER2-positive carcinoma in the breast. Disitamab vedotin (RC48) is a newly developed ADC drug targeting HER2 that is comprised of hertuzumab coupling monomethyl auristatin E (MMAE) via a cleavable linker. This paper aims to offer a general insight and summary of the mechanism of action and the currently completed and ongoing clinical studies of RC-48 in HER-2 positive solid tumors.     

洛泊妥珠单抗不良反应的回顾性分析

目的 分析洛泊妥珠单抗所致不良反应(adverse drug reaction,ADR)的发生情况及临床特点,为临床合理用药提供参考。方法 检索医院信息系统,收集2021年以来在我院住院并使用洛泊妥珠单抗的所有患者的病历资料,记录患者基本信息、用药情况、不良反应发生情况等,进行回顾性分析。结果 纳入分析的患者共7例,其中男性4例(57.1%)、女性3例(42.8%),主要ADRs包括中性粒细胞减少、感染、胃肠道反应,以及不太常见的呼吸系统疾病。ADRs主要发生在首次用药后3个月内,经对症治疗或观察等待后均可恢复,未发生因不良反应死亡病例。结论 临床合理使用洛泊妥珠单抗时,应提高临床工作者对不良反应的监测,保障患者用药物安全性。     

A safety evaluation of brentuximab vedotin for the treatment of Hodgkin lymphoma

ABSTRACT

Introduction: Brentuximab vedotin is an anti-CD30 monoclonal antibody-drug conjugate approved for treating relapsed or refractory Hodgkin lymphoma. The pivotal trial demonstrated brentuximab vedotin’s efficacy and manageable toxicity profile with peripheral neuropathy and neutropenia being the most common side effects. The phase I study of brentuximab vedotin combined with ABVD or AVD revealed its contraindication with bleomycin due to pulmonary toxicity. As trials continue to investigate the drug in frontline and relapsed settings, emerging safety data will further define brentuximab vedotin’s role in managing Hodgkin lymphoma.

Areas covered: This article reviews the current literature on brentuximab vedotin in Hodgkin lymphoma treatment, both as a single agent and in combination regimens. The review focuses on safety findings from clinical trials, expected adverse events, and rare serious toxicities.

Expert opinion: Brentuximab vedotin is a breakthrough antibody-drug conjugate that may provide new options in earlier lines of therapy for Hodgkin lymphoma. Results from the ongoing phase III trial comparing ABVD to AVD + brentuximab vedotin will inform whether brentuximab vedotin adds benefit to frontline therapy over the current standard of care. The optimal duration of treatment and brentuximab vedotin’s potential as an alternative to radiation in early stage disease still warrant investigation.     

治疗晚期或转移性尿路上皮癌的抗体偶联药物:enfortumab vedotin

enfortumab vedotin为一种抗体偶联药物,可与nectin-4结合释放出小分子细胞毒药物单甲基奥瑞他汀E。单甲基奥瑞他汀E具有抗有丝分裂的作用,能作用于微管蛋白抑制肿瘤生长。enfortumab vedotin可用于治疗晚期或转移性尿路上皮癌。常见不良反应有疲劳、外周神经病变、食欲下降、皮疹等。     

Brentuximab Vedotin (SGN-35), an antibody-drug conjugate for the treatment of CD30-positive malignancies

INTRODUCTION: CD30-positive hematological malignancies are potentially curable with frontline combination chemotherapy regimens; however, those patients who relapse or are refractory to initial therapies have less favorable prognosis. AREAS COVERED: Brentuximab vedotin is an antibody-drug conjugate (ADC) composed of the anti-CD30 chimeric IgG1 monoclonal antibody cAC10 and the potent antimicrotubule drug monomethylauristatin E connected by a protease-cleavable linker. Treatment with single-agent brentuximab vedotin resulted in unprecedented objective response rates and complete response rates of 75 and 34%, respectively, in relapsed or refractory Hodgkin lymphoma, and of 86 and 57%, respectively, in relapsed or refractory systemic anaplastic large-cell lymphoma patients. Peripheral sensory neuropathy and neutropenia were observed with brentuximab vedotin but were generally grade 1 and 2 in severity and manageable. In August 2011, brentuximab vedotin was approved in the US for the treatment of Hodgkin lymphoma after failure of autologous stem cell transplant (ASCT) or after failure of at least two prior multiagent chemotherapy regimens in ASCT-ineligible candidates, and for the treatment of systemic anaplastic large-cell lymphoma after failure of at least one prior multiagent chemotherapy regimen. EXPERT OPINION: These data support an expanded development program for brentuximab vedotin in multiple CD30-positive indications.