Seminars in hematology最新文献

英文中文

Tuning CAR T-cell therapies for efficacy and reduced toxicity 调整 CAR T 细胞疗法，提高疗效并降低毒性

IF 5 3区医学 Q1 HEMATOLOGY

Seminars in hematology

Pub Date : 2024-10-01 DOI: 10.1053/j.seminhematol.2024.07.003

Danielle Blud , Patricia Rubio-Reyes , Rachel Perret , Robert Weinkove

Chimeric antigen receptor (CAR) T-cell therapies are a standard of care for certain relapsed or refractory B-cell cancers. However, many patients do not respond to CAR T-cell therapy or relapse later, short- and long-term toxicities are common, and current CAR T-cell therapies have limited efficacy for solid cancers. The gene engineering inherent in CAR T-cell manufacture offers an unprecedented opportunity to control cellular characteristics and design products that may overcome these limitations. This review summarises available methods to “tune” CAR T-cells for optimal efficacy and safety. The components of a typical CAR, and the modifications that can influence CAR T-cell function are discussed. Methods of engineering passive, inducible or autonomous control mechanisms into CAR T-cells, allowing selective limitation or enhancement of CAR T-cell activity are reviewed. The impact of manufacturing processes on CAR T-cell function are considered, including methods of limiting CAR T-cell terminal differentiation and exhaustion, and the use of specific T-cell subsets as the CAR T starting material. We discuss the use of multicistronic transgenes and multiplexed gene editing. Finally, we highlight the need for innovative clinical trial designs if we are to make the most of the opportunities offered by CAR T-cell therapies.

嵌合抗原受体（CAR）T 细胞疗法是治疗某些复发或难治性 B 细胞癌症的标准疗法。然而，许多患者对 CAR T 细胞疗法没有反应或稍后复发，短期和长期毒性反应很常见，而且目前的 CAR T 细胞疗法对实体瘤的疗效有限。CAR T 细胞制造中固有的基因工程技术为控制细胞特性和设计可克服这些限制的产品提供了前所未有的机会。本综述总结了 "调整 "CAR T 细胞以获得最佳疗效和安全性的现有方法。本文讨论了典型 CAR 的组成成分以及可影响 CAR T 细胞功能的修饰。综述了在 CAR T 细胞中植入被动、可诱导或自主控制机制的方法，从而有选择性地限制或增强 CAR T 细胞的活性。我们还考虑了制造过程对 CAR T 细胞功能的影响，包括限制 CAR T 细胞末端分化和衰竭的方法，以及使用特定 T 细胞亚群作为 CAR T 细胞的起始材料。我们还讨论了多序列转基因和多重基因编辑的使用。最后，我们强调了创新临床试验设计的必要性，只有这样才能充分利用 CAR T 细胞疗法带来的机遇。

{"title":"Tuning CAR T-cell therapies for efficacy and reduced toxicity","authors":"Danielle Blud , Patricia Rubio-Reyes , Rachel Perret , Robert Weinkove","doi":"10.1053/j.seminhematol.2024.07.003","DOIUrl":"10.1053/j.seminhematol.2024.07.003","url":null,"abstract":"<div><div>Chimeric antigen receptor (CAR) T-cell therapies are a standard of care for certain relapsed or refractory B-cell cancers. However, many patients do not respond to CAR T-cell therapy or relapse later, short- and long-term toxicities are common, and current CAR T-cell therapies have limited efficacy for solid cancers. The gene engineering inherent in CAR T-cell manufacture offers an unprecedented opportunity to control cellular characteristics and design products that may overcome these limitations. This review summarises available methods to “tune” CAR T-cells for optimal efficacy and safety. The components of a typical CAR, and the modifications that can influence CAR T-cell function are discussed. Methods of engineering passive, inducible or autonomous control mechanisms into CAR T-cells, allowing selective limitation or enhancement of CAR T-cell activity are reviewed. The impact of manufacturing processes on CAR T-cell function are considered, including methods of limiting CAR T-cell terminal differentiation and exhaustion, and the use of specific T-cell subsets as the CAR T starting material. We discuss the use of multicistronic transgenes and multiplexed gene editing. Finally, we highlight the need for innovative clinical trial designs if we are to make the most of the opportunities offered by CAR T-cell therapies.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 5","pages":"Pages 333-344"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141713143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

License for a CAR T: Examining patient eligibility CAR T 许可：审查患者资格

IF 5 3区医学 Q1 HEMATOLOGY

Seminars in hematology

Pub Date : 2024-10-01 DOI: 10.1053/j.seminhematol.2024.07.001

Neha Akkad , Dai Chihara

Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment landscape of lymphoma and is now approved by the FDA for multiple indications. Given that the indications for CAR T-cell therapy are expanding, a larger patient population will be eligible to receive this treatment in the coming years. Pivotal clinical trials leading to FDA approval of CAR T-cell products required patients to have adequate organ function and good performance status. In the real world, however, the patient population eligible for CAR T-cell therapy includes patients who are older, frail, have poor performance status, and have multiple comorbidities. Studies have shown that CAR T-cell therapy is relatively safe and tolerable in such frail patients, however, there is no agreed upon consensus or guidelines to assess eligibility for CAR T-cell therapy at this moment. Gaining further insight into such patient populations will be vital in order to safely provide and expand access to CAR T-cell therapy.

嵌合抗原受体（CAR）T 细胞疗法改变了淋巴瘤的治疗格局，目前已获美国食品及药物管理局批准用于多种适应症。鉴于 CAR T 细胞疗法的适应症在不断扩大，未来几年将有更多的患者有资格接受这种治疗。导致 FDA 批准 CAR T 细胞产品的关键临床试验要求患者有足够的器官功能和良好的表现状态。但在现实世界中，符合 CAR T 细胞疗法条件的患者群体包括年老体弱、表现不佳和患有多种并发症的患者。研究表明，CAR T 细胞疗法对这类体弱患者相对安全且可耐受，但目前还没有达成一致的共识或指南来评估接受 CAR T 细胞疗法的资格。要想安全地提供 CAR T 细胞疗法并扩大其使用范围，进一步了解这类患者群体至关重要。

引用次数: 0

Mobilizing CARs: Benefits, drawbacks, and directions for outpatient CAR T-cell therapy 调动 CAR：门诊 CAR T 细胞疗法的优点、缺点和发展方向。

IF 5 3区医学 Q1 HEMATOLOGY

Seminars in hematology

Pub Date : 2024-10-01 DOI: 10.1053/j.seminhematol.2024.08.003

Jennifer S. Woo , Kim Nguyen , Lawrence Liu , Amrita Krishnan , Tanya Siddiqi , Azra Borogovac

Chimeric antigen receptor T-cell (CAR-T) therapy has heralded a new era in the treatment of various hematological malignancies, increasingly being utilized in earlier lines of therapy. Moreover, cellular therapies are currently under investigation for their potential in treating solid malignancies and autoimmune disorders. As the scope of indications for CAR-T therapy continues to expand, along with the associated reductions in costs and hospital admissions, many medical centers are transitioning towards outpatient CAR-T models. Moreover, ongoing efforts to mitigate complications such as cytokine release syndrome (CRS) or neurotoxicity include the development of premedication strategies, prompt management of adverse events, and the advancement of newer, safer CAR-T cell therapies. However, despite these advancements, the inherent risk of these life-threatening complications remains a critical concern in CAR-T therapy. Institutions must diligently anticipate and effectively manage these complications to ensure the safety and well-being of patients undergoing CAR-T therapy. This includes establishing robust protocols for timely identification and intervention of adverse events, and seamless pathways for transitioning patients to a higher level of care if necessary. This review provides an overview of the current landscape of outpatient CAR-T therapy and offers essential insights into the key clinical and operational considerations needed to implement a successful outpatient CAR-T program.

嵌合抗原受体 T 细胞（CAR-T）疗法开创了治疗各种血液恶性肿瘤的新纪元，越来越多地用于早期治疗。此外，目前正在研究细胞疗法在治疗实体恶性肿瘤和自身免疫性疾病方面的潜力。随着 CAR-T 疗法适应症范围的不断扩大，以及相关费用和住院率的降低，许多医疗中心正在向门诊 CAR-T 模式过渡。此外，为减少细胞因子释放综合征（CRS）或神经毒性等并发症，正在进行的努力包括制定前期用药策略、及时处理不良事件以及开发更新、更安全的 CAR-T 细胞疗法。然而，尽管取得了这些进步，这些危及生命的并发症的固有风险仍然是 CAR-T 疗法的关键问题。医疗机构必须努力预测并有效控制这些并发症，以确保接受 CAR-T 疗法的患者的安全和健康。这包括建立健全的方案，及时发现和干预不良事件，以及在必要时将患者转至更高水平治疗的无缝路径。本综述概述了门诊 CAR-T 疗法的现状，并就成功实施门诊 CAR-T 计划所需的关键临床和操作注意事项提供了重要见解。

{"title":"Mobilizing CARs: Benefits, drawbacks, and directions for outpatient CAR T-cell therapy","authors":"Jennifer S. Woo , Kim Nguyen , Lawrence Liu , Amrita Krishnan , Tanya Siddiqi , Azra Borogovac","doi":"10.1053/j.seminhematol.2024.08.003","DOIUrl":"10.1053/j.seminhematol.2024.08.003","url":null,"abstract":"<div><div>Chimeric antigen receptor T-cell (CAR-T) therapy has heralded a new era in the treatment of various hematological malignancies, increasingly being utilized in earlier lines of therapy. Moreover, cellular therapies are currently under investigation for their potential in treating solid malignancies and autoimmune disorders. As the scope of indications for CAR-T therapy continues to expand, along with the associated reductions in costs and hospital admissions, many medical centers are transitioning towards outpatient CAR-T models. Moreover, ongoing efforts to mitigate complications such as cytokine release syndrome (CRS) or neurotoxicity include the development of premedication strategies, prompt management of adverse events, and the advancement of newer, safer CAR-T cell therapies. However, despite these advancements, the inherent risk of these life-threatening complications remains a critical concern in CAR-T therapy. Institutions must diligently anticipate and effectively manage these complications to ensure the safety and well-being of patients undergoing CAR-T therapy. This includes establishing robust protocols for timely identification and intervention of adverse events, and seamless pathways for transitioning patients to a higher level of care if necessary. This review provides an overview of the current landscape of outpatient CAR-T therapy and offers essential insights into the key clinical and operational considerations needed to implement a successful outpatient CAR-T program.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 5","pages":"Pages 273-283"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142353083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fast and furious: Changing gears on the road to cure with chimeric antigen receptor T cells in multiple myeloma 速度与激情：利用嵌合抗原受体 T 细胞治疗多发性骨髓瘤，在治愈之路上换挡加速

IF 5 3区医学 Q1 HEMATOLOGY

Seminars in hematology

Pub Date : 2024-10-01 DOI: 10.1053/j.seminhematol.2024.07.002

Nico Gagelmann , Maximilian Merz

Based on the pivotal KarMMa-1 and CARTITUDE-1 studies, Idecabtagene vicleucel (Ide-cel) and Ciltacabtagene autoleucel (Cilta-cel) have been approved to treat multiple myeloma patients, who have been exposed to at least 1 proteasome inhibitor, immunomodulatory drug and anti-CD38 antibody after 4 or 3 lines of therapy, respectively. The unprecedented rates of deep and long-lasting remissions have been meanwhile confirmed in multiple real-world analyses and more recently, the KarMMa-3 and CARTITUDE-4 studies lead to the approval in earlier lines of therapy. It is currently believed that ultimately all patients with relapsed/refractory multiple myeloma experience relapse after anti-BCMA CAR T-cell therapies. There is a plethora of CAR T-cell therapies targeting novel antigens, with the aim to overcome current CAR T-cell resistance. In this review, we will summarize current evidence of novel antigens and their clinical potential. Together with current CAR T-cell therapy and T-cell engagers, these approaches might lead us to the next frontier in multiple myeloma: total immunotherapy and the road to chemotherapy-free cure.

基于关键性的 KarMMa-1 和 CARTITUDE-1 研究，Idecabtagene vicleucel（Ide-cel）和 Ciltacabtagene autoleucel（Cilta-cel）已被批准用于治疗多发性骨髓瘤患者，这些患者在接受 4 或 3 个疗程的治疗后，至少已使用过一种蛋白酶体抑制剂、免疫调节药物和抗 CD38 抗体。同时，该疗法前所未有的深度和持久缓解率在多项实际分析中得到了证实，最近，KarMMa-3 和 CARTITUDE-4 研究又促使该疗法在更早的治疗方案中获得批准。目前认为，所有复发/难治性多发性骨髓瘤患者在接受抗 BCMA CAR T 细胞疗法后最终都会复发。目前有大量以新型抗原为靶点的 CAR T 细胞疗法，目的是克服目前的 CAR T 细胞耐药性。在本综述中，我们将总结目前新型抗原的证据及其临床潜力。这些方法与目前的CAR T细胞疗法和T细胞吞噬剂一起，可能会引领我们进入多发性骨髓瘤的下一个前沿领域：全面免疫疗法和无化疗治愈之路。

{"title":"Fast and furious: Changing gears on the road to cure with chimeric antigen receptor T cells in multiple myeloma","authors":"Nico Gagelmann , Maximilian Merz","doi":"10.1053/j.seminhematol.2024.07.002","DOIUrl":"10.1053/j.seminhematol.2024.07.002","url":null,"abstract":"<div><div>Based on the pivotal KarMMa-1 and CARTITUDE-1 studies, Idecabtagene vicleucel (Ide-cel) and Ciltacabtagene autoleucel (Cilta-cel) have been approved to treat multiple myeloma patients, who have been exposed to at least 1 proteasome inhibitor, immunomodulatory drug and anti-CD38 antibody after 4 or 3 lines of therapy, respectively. The unprecedented rates of deep and long-lasting remissions have been meanwhile confirmed in multiple real-world analyses and more recently, the KarMMa-3 and CARTITUDE-4 studies lead to the approval in earlier lines of therapy. It is currently believed that ultimately all patients with relapsed/refractory multiple myeloma experience relapse after anti-BCMA CAR T-cell therapies. There is a plethora of CAR T-cell therapies targeting novel antigens, with the aim to overcome current CAR T-cell resistance. In this review, we will summarize current evidence of novel antigens and their clinical potential. Together with current CAR T-cell therapy and T-cell engagers, these approaches might lead us to the next frontier in multiple myeloma: total immunotherapy and the road to chemotherapy-free cure.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 5","pages":"Pages 306-313"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141696986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The pediatric approach to Hodgkin lymphoma 霍奇金淋巴瘤的儿科治疗方法

IF 5 3区医学 Q1 HEMATOLOGY

Seminars in hematology

Pub Date : 2024-08-01 DOI: 10.1053/j.seminhematol.2024.05.003

Hodgkin lymphoma (HL) occurs throughout the lifespan but is one of the most common cancers in adolescents and young adults (AYA; 15-39 years). HL has become a highly curable disease with survival rates surpassing 90%, including patients with high-risk and advanced stage disease. Unfortunately, intensive treatment carries a risk of short- and long-term toxicity. Given the decades pediatric HL survivors are expected to live after treatment, the pediatric approach to treatment has focused on improving the therapeutic index through response adapted treatment and more recently the incorporation of novel agents. The efforts of pediatric and medical oncologists in research and clinical trial development have long occurred in parallel, but recent efforts have laid the foundation for collaboration with the goal of standardizing AYA care and allowing earlier incorporation of novel therapy for younger patients. This review focuses on the evolution of the management of pediatric HL including epidemiology, biology, and approaches to upfront and salvage treatment regimens.

霍奇金淋巴瘤（HL）在人的一生中都会发生，但它是青少年和年轻人（AYA；15-39 岁）中最常见的癌症之一。HL 已成为一种高度可治愈的疾病，存活率超过 90%，包括高危和晚期患者。遗憾的是，强化治疗存在短期和长期毒性风险。鉴于小儿 HL 幸存者在接受治疗后预计可存活数十年，儿科治疗方法侧重于通过适应反应治疗以及最近采用的新型药物来提高治疗指数。长期以来，儿科和肿瘤内科医生在研究和临床试验开发方面的工作一直并行不悖，但最近的工作为双方的合作奠定了基础，其目标是实现青壮年治疗的标准化，并为年轻患者更早地采用新型疗法。本综述重点介绍儿科 HL 管理的演变，包括流行病学、生物学以及前期和挽救性治疗方案的方法。

引用次数: 0

Molecular biomarkers in classic Hodgkin lymphoma 典型霍奇金淋巴瘤的分子生物标志物。

IF 5 3区医学 Q1 HEMATOLOGY

Seminars in hematology

Pub Date : 2024-08-01 DOI: 10.1053/j.seminhematol.2024.05.005

Classic Hodgkin lymphoma is a unique B-cell derived malignancy featuring rare malignant Hodgkin and Reed Sternberg (HRS) cells that are embedded in a quantitively dominant tumor microenvironment (TME). Treatment of classic Hodgkin lymphoma has significantly evolved in the past decade with improving treatment outcomes for newly diagnosed patients and the minority of patients suffering from disease progression. However, the burden of toxicity and treatment-related long-term sequelae remains high in a typically young patient population. This highlights the need for better molecular biomarkers aiding in risk-adapted treatment strategies and predicting response to an increasing number of available treatments that now prominently involve multiple immunotherapy options. Here, we review modern molecular biomarker approaches that reflect both the biology of the malignant HRS cells and cellular components in the TME, while holding the promise to improve diagnostic frameworks for clinical decision-making and be feasible in clinical trials and routine practice. In particular, technical advances in sequencing and analytic pipelines using liquid biopsies, as well as deep phenotypic characterization of tissue architecture at single-cell resolution, have emerged as the new frontier of biomarker development awaiting further validation and implementation in routine diagnostic procedures.

典型霍奇金淋巴瘤是一种独特的B细胞衍生恶性肿瘤，其特征是罕见的恶性霍奇金和里德-斯登伯格（HRS）细胞嵌入数量占优势的肿瘤微环境（TME）中。在过去十年中，经典霍奇金淋巴瘤的治疗有了长足的发展，新诊断患者和少数疾病进展期患者的治疗效果不断改善。然而，在典型的年轻患者群体中，毒性和与治疗相关的长期后遗症的负担仍然很高。这凸显了对更好的分子生物标记物的需求，这些标记物有助于制定风险适应性治疗策略，并预测对越来越多的可用治疗方法的反应，这些治疗方法目前主要包括多种免疫疗法。在此，我们回顾了反映恶性 HRS 细胞生物学特性和 TME 中细胞成分的现代分子生物标志物方法，这些方法有望改善临床决策的诊断框架，并在临床试验和常规实践中具有可行性。尤其是利用液体活检进行测序和分析管道的技术进步，以及单细胞分辨率的组织结构深度表型特征描述，已成为生物标记开发的新前沿，有待进一步验证并在常规诊断程序中实施。

{"title":"Molecular biomarkers in classic Hodgkin lymphoma","authors":"","doi":"10.1053/j.seminhematol.2024.05.005","DOIUrl":"10.1053/j.seminhematol.2024.05.005","url":null,"abstract":"<div><p><span><span>Classic Hodgkin lymphoma<span> is a unique B-cell derived malignancy<span> featuring rare malignant Hodgkin and Reed Sternberg (HRS) cells that are embedded in a quantitively dominant tumor microenvironment (TME). Treatment of classic Hodgkin lymphoma has significantly evolved in the past decade with improving treatment outcomes for newly diagnosed patients and the minority of patients suffering from </span></span></span>disease progression<span><span>. However, the burden of toxicity and treatment-related long-term sequelae remains high in a typically young patient population. This highlights the need for better molecular biomarkers aiding in risk-adapted treatment strategies and predicting response to an increasing number of available treatments that now prominently involve multiple </span>immunotherapy<span> options. Here, we review modern molecular biomarker approaches that reflect both the biology of the malignant HRS cells and cellular components in the TME, while holding the promise to improve diagnostic frameworks for clinical decision-making and be feasible in clinical trials and routine practice. In particular, technical advances in sequencing and analytic pipelines using </span></span></span>liquid biopsies, as well as deep phenotypic characterization of tissue architecture at single-cell resolution, have emerged as the new frontier of biomarker development awaiting further validation and implementation in routine diagnostic procedures.</p></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 4","pages":"Pages 221-228"},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of autologous stem-cell transplantation in classical Hodgkin lymphoma in the modern era 现代自体干细胞移植在经典霍奇金淋巴瘤中的作用。

IF 5 3区医学 Q1 HEMATOLOGY

Seminars in hematology

Pub Date : 2024-08-01 DOI: 10.1053/j.seminhematol.2024.06.003

Gaurav Varma , Catherine Diefenbach

Despite excellent cure rates with modern front-line regimens, up to 20% of patients with Hodgkin lymphoma will progress through front-line therapy or experience disease relapse. Worldwide, salvage chemotherapy followed by high-dose chemotherapy with autologous stem cell transplantation (HDT/ASCT) is considered the standard of care for these patients and can cure approximately 50% of relapsed or refractory (R/R) patients in the second line. Brentuximab vedotin (BV), an anti-CD30 antibody drug conjugate, and PD1 inhibitors like nivolumab and pembrolizumab, have high response rates in patients who recur after HDT/ASCT. When used prior to HDT/ASCT, BV and PD1 inhibitors appear to dramatically increase the effectiveness of salvage therapies with complete response rates often double those seen with historic chemotherapy-based regimens and durable progression free survival (PFS) post-HDT/ASCT. Emerging data in adults and from pediatric trials showing a durable PFS in a subset of relapsed patients raises the question of whether HDT/ASCT is essential for cure in R/R patients after PD1 based salvage. Future studies will help clarify if ASCT can omitted PD1 based salvage to avoid the potential toxicity of HDT/ASCT without compromising cure.

尽管现代一线治疗方案的治愈率极高，但仍有高达20%的霍奇金淋巴瘤患者会在一线治疗后病情恶化或复发。在全球范围内，抢救性化疗后进行大剂量化疗和自体干细胞移植（HDT/ASCT）被认为是这些患者的标准治疗方法，在二线治疗中可治愈约50%的复发或难治（R/R）患者。抗 CD30 抗体药物共轭物 Brentuximab vedotin (BV) 和 PD1 抑制剂（如 nivolumab 和 pembrolizumab）对 HDT/ASCT 后复发的患者有很高的应答率。在 HDT/ASCT 前使用 BV 和 PD1 抑制剂似乎能显著提高挽救疗法的疗效，其完全应答率通常是以往化疗方案的两倍，并且在 HDT/ASCT 后能获得持久的无进展生存期（PFS）。成人和儿科试验中新出现的数据显示，复发患者中的一部分人可获得持久的 PFS，这就提出了一个问题：在基于 PD1 的挽救治疗后，HDT/ASCT 是否是 R/R 患者治愈的必要条件。未来的研究将有助于明确 ASCT 是否可以省略基于 PD1 的挽救治疗，以避免 HDT/ASCT 的潜在毒性，同时又不影响治愈。

{"title":"The role of autologous stem-cell transplantation in classical Hodgkin lymphoma in the modern era","authors":"Gaurav Varma , Catherine Diefenbach","doi":"10.1053/j.seminhematol.2024.06.003","DOIUrl":"10.1053/j.seminhematol.2024.06.003","url":null,"abstract":"<div><p><span><span><span>Despite excellent cure rates with modern front-line regimens, up to 20% of patients with Hodgkin lymphoma will progress through front-line therapy or experience disease relapse. Worldwide, salvage chemotherapy followed by high-dose chemotherapy with </span>autologous stem cell transplantation<span> (HDT/ASCT) is considered the standard of care for these patients and can cure approximately 50% of relapsed or refractory (R/R) patients in the second line. Brentuximab vedotin (BV), an anti-CD30 </span></span>antibody drug conjugate, and PD1 inhibitors like </span>nivolumab<span> and pembrolizumab<span><span><span>, have high response rates in patients who recur after HDT/ASCT. When used prior to HDT/ASCT, BV and PD1 inhibitors appear to dramatically increase the effectiveness of salvage therapies with complete response rates often double those seen with historic chemotherapy-based regimens and durable </span>progression free survival (PFS) post-HDT/ASCT. Emerging data in adults and from </span>pediatric trials showing a durable PFS in a subset of relapsed patients raises the question of whether HDT/ASCT is essential for cure in R/R patients after PD1 based salvage. Future studies will help clarify if ASCT can omitted PD1 based salvage to avoid the potential toxicity of HDT/ASCT without compromising cure.</span></span></p></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 4","pages":"Pages 253-262"},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of response adapted therapy in the era of novel agents 新型药物时代反应适应疗法的作用

IF 5 3区医学 Q1 HEMATOLOGY

Seminars in hematology

Pub Date : 2024-08-01 DOI: 10.1053/j.seminhematol.2024.06.002

The optimal treatment of classic Hodgkin Lymphoma (cHL) requires an individualized approach, with therapy guided by pretreatment clinical risk stratification and interim response assessment with positron emission tomography (PET). The overall goal is to achieve high cure rates while minimizing acute toxicity and late therapy-related effects. Interim PET-adapted strategies (iPET) were initially developed with traditional chemotherapy, reducing intensity after interim complete response and escalating treatment for patients with iPET+ disease. Recently, novel agents including brentuximab vedotin and the checkpoint inhibitor immunotherapies (CPIs) pembrolizumab and nivolumab have been adopted into the front-line treatment of cHL, and PET-adapted approaches may be relevant for these drugs as well. In this review we discuss response-adapted strategies utilizing novel agents, consider challenges including indeterminate radiographic findings with CPIs, and address emerging techniques for response assessment including new PET-based imaging metrics and the role of circulating tumor DNA.

典型霍奇金淋巴瘤（cHL）的最佳治疗需要个体化方法，治疗以治疗前临床风险分层和正电子发射断层扫描（PET）中期反应评估为指导。总体目标是在实现高治愈率的同时，尽量减少急性毒性和后期治疗相关的影响。正电子发射断层扫描中期适应策略（iPET）最初是与传统化疗一起开发的，在中期完全反应后降低化疗强度，并对 iPET+ 疾病患者进行升级治疗。最近，包括 brentuximab vedotin 和检查点抑制剂免疫疗法（CPIs）pembrolizumab 和 nivolumab 在内的新型药物已被采用到 cHL 的一线治疗中，PET 适应方法也可能与这些药物相关。在这篇综述中，我们将讨论利用新型药物的反应适应策略，考虑包括 CPIs 影像学结果不确定在内的挑战，并探讨新出现的反应评估技术，包括新的基于 PET 的成像指标和循环肿瘤 DNA 的作用。

{"title":"The role of response adapted therapy in the era of novel agents","authors":"","doi":"10.1053/j.seminhematol.2024.06.002","DOIUrl":"10.1053/j.seminhematol.2024.06.002","url":null,"abstract":"<div><p><span><span>The optimal treatment of classic Hodgkin Lymphoma (cHL) requires an individualized approach, with therapy guided by pretreatment clinical </span>risk stratification<span> and interim response assessment with positron emission tomography (PET). The overall goal is to achieve high cure rates while minimizing </span></span>acute toxicity<span><span> and late therapy-related effects. Interim PET-adapted strategies (iPET) were initially developed with traditional chemotherapy, reducing intensity after interim complete response and escalating treatment for patients with iPET+ disease. Recently, novel agents including brentuximab vedotin and the checkpoint inhibitor </span>immunotherapies<span><span> (CPIs) pembrolizumab and </span>nivolumab<span> have been adopted into the front-line treatment of cHL, and PET-adapted approaches may be relevant for these drugs as well. In this review we discuss response-adapted strategies utilizing novel agents, consider challenges including indeterminate radiographic findings with CPIs, and address emerging techniques for response assessment including new PET-based imaging metrics and the role of circulating tumor DNA.</span></span></span></p></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 4","pages":"Pages 229-235"},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141414785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

outside front cover, PMS 8883 metallic AND 4/C 封面外侧，PMS 8883 金属色和 4/C

IF 5 3区医学 Q1 HEMATOLOGY

Seminars in hematology

Pub Date : 2024-08-01 DOI: 10.1053/S0037-1963(24)00093-3

引用次数: 0

Challenges for HL in the modern era: Questions to move the field forward 现代人类学面临的挑战：推动该领域发展的问题

IF 5 3区医学 Q1 HEMATOLOGY

Seminars in hematology

Pub Date : 2024-08-01 DOI: 10.1053/j.seminhematol.2024.09.002

Catherine Diefenbach MD

引用次数: 0

首页上一页

下一页尾页

类型

全部化学•材料生命科学医学物理工程技术环境•农林材料科学地球科学法学管理学化学环境科学与生态学计算机科学教育学经济学农林科学人文科学生物学数学物理与天体物理心理学综合性期刊其他工业工程理学历史学农学文学信息工程

数据库

全部 ACS Publications Elsevier ieeexplore Springer The Royal Society of Chemistry Wiley

期刊

Seminars in hematology

全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.

﹀