Pub Date : 2024-10-18DOI: 10.1053/j.seminhematol.2024.10.002
Roshani Patel, Elizabeth Hill, Madhav Dhodapkar
Smoldering multiple myeloma (SMM) was first described over 40 years ago yet much is still unknown including which patients will ultimately progress to symptomatic multiple myeloma (MM). The genetics of the premalignant clone and the immune microenvironment in which it exists is now well understood to both play a role in disease progression. However, the clinical risk models available to help identify patients at most risk of progression still rely primarily on data reflecting volume of disease rather than underlying biology. While it is of upmost importance to accurately diagnose patients with SMM to avoid over or under treatment, efforts are ongoing to tease out if early intervention is indeed warranted for a subgroup of patients with SMM. This article will review the history and biology of SMM, discuss the utility of existing risk models, and examine the efforts to date which have challenged standard management.
{"title":"Smoldering multiple myeloma: Integrating biology and risk into management.","authors":"Roshani Patel, Elizabeth Hill, Madhav Dhodapkar","doi":"10.1053/j.seminhematol.2024.10.002","DOIUrl":"https://doi.org/10.1053/j.seminhematol.2024.10.002","url":null,"abstract":"<p><p>Smoldering multiple myeloma (SMM) was first described over 40 years ago yet much is still unknown including which patients will ultimately progress to symptomatic multiple myeloma (MM). The genetics of the premalignant clone and the immune microenvironment in which it exists is now well understood to both play a role in disease progression. However, the clinical risk models available to help identify patients at most risk of progression still rely primarily on data reflecting volume of disease rather than underlying biology. While it is of upmost importance to accurately diagnose patients with SMM to avoid over or under treatment, efforts are ongoing to tease out if early intervention is indeed warranted for a subgroup of patients with SMM. This article will review the history and biology of SMM, discuss the utility of existing risk models, and examine the efforts to date which have challenged standard management.</p>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740422","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}
Pub Date : 2024-10-05DOI: 10.1053/j.seminhematol.2024.10.001
Zachary M Avigan, Constantine S Mitsiades, Alessandro Laganà
Chromosome 1q copy number variations, collectively termed +1q, are 1 of the most common cytogenetic abnormalities in multiple myeloma. 1q abnormalities are associated with overexpression of a high-risk gene signature promoting cell proliferation, apoptosis resistance, genomic instability, and treatment resistance, and acquisition or expansion of +1q subclones mediate disease development and relapse. While there remains significant controversy as to whether the presence of +1q is itself an independent driver of poor prognosis or is simply a marker of other high-risk features, +1q has recently been incorporated into multiple prognostic scoring models as a new high-risk cytogenetic abnormality. In this review, we present possible underlying genetic mechanisms of high-risk disease in +1q myeloma, implications for subclonal development, its role in modifying the tumor microenvironment, current evidence for clinical significance in newly-diagnosed and relapsed patients, and current controversies in +1q classification and prognostication.
{"title":"The role of 1q abnormalities in multiple myeloma: Genomic insights, clinical implications, and therapeutic challenges.","authors":"Zachary M Avigan, Constantine S Mitsiades, Alessandro Laganà","doi":"10.1053/j.seminhematol.2024.10.001","DOIUrl":"https://doi.org/10.1053/j.seminhematol.2024.10.001","url":null,"abstract":"<p><p>Chromosome 1q copy number variations, collectively termed +1q, are 1 of the most common cytogenetic abnormalities in multiple myeloma. 1q abnormalities are associated with overexpression of a high-risk gene signature promoting cell proliferation, apoptosis resistance, genomic instability, and treatment resistance, and acquisition or expansion of +1q subclones mediate disease development and relapse. While there remains significant controversy as to whether the presence of +1q is itself an independent driver of poor prognosis or is simply a marker of other high-risk features, +1q has recently been incorporated into multiple prognostic scoring models as a new high-risk cytogenetic abnormality. In this review, we present possible underlying genetic mechanisms of high-risk disease in +1q myeloma, implications for subclonal development, its role in modifying the tumor microenvironment, current evidence for clinical significance in newly-diagnosed and relapsed patients, and current controversies in +1q classification and prognostication.</p>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558720","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}
Pub Date : 2024-10-01DOI: 10.1053/j.seminhematol.2024.08.005
Omar Castaneda Puglianini , Julio C. Chavez
Chimeric antigen receptor T-cell (CAR-T) has revolutionized the treatment of hematologic malignancies. There are several approvals in lymphomas, leukemias and myeloma. Randomized clinical trials have shown that CAR-T cell therapy improves survival over standard of care in diffuse large B-cell lymphoma (DLBCL) and multiple myeloma (MM), changing dramatically the current treatment paradigm. Current efforts are directed in improving outcomes in the frontline setting and confirmatory randomized trials are ongoing.
嵌合抗原受体 T 细胞（CAR-T）彻底改变了血液系统恶性肿瘤的治疗。目前已有数种淋巴瘤、白血病和骨髓瘤获得批准。随机临床试验表明，与标准疗法相比，CAR-T 细胞疗法提高了弥漫大 B 细胞淋巴瘤（DLBCL）和多发性骨髓瘤（MM）的生存率，极大地改变了目前的治疗模式。目前的努力方向是改善一线治疗的疗效，确证性随机试验正在进行中。
{"title":"CARs Moving Forward: The Development of CAR T-Cell Therapy in the Earlier Treatment Course of Hematologic Malignancies","authors":"Omar Castaneda Puglianini , Julio C. Chavez","doi":"10.1053/j.seminhematol.2024.08.005","DOIUrl":"10.1053/j.seminhematol.2024.08.005","url":null,"abstract":"<div><div>Chimeric antigen receptor T-cell (CAR-T) has revolutionized the treatment of hematologic malignancies. There are several approvals in lymphomas, leukemias and myeloma. Randomized clinical trials have shown that CAR-T cell therapy improves survival over standard of care in diffuse large B-cell lymphoma (DLBCL) and multiple myeloma (MM), changing dramatically the current treatment paradigm. Current efforts are directed in improving outcomes in the frontline setting and confirmatory randomized trials are ongoing.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 5","pages":"Pages 290-296"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294510","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}
Pub Date : 2024-10-01DOI: 10.1053/j.seminhematol.2024.10.003
Jennifer N. Brudno MD
{"title":"CAR T-cell therapy comes of age: Introductory editorial for the special issue","authors":"Jennifer N. Brudno MD","doi":"10.1053/j.seminhematol.2024.10.003","DOIUrl":"10.1053/j.seminhematol.2024.10.003","url":null,"abstract":"","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 5","pages":"Pages 271-272"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438241","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}
Pub Date : 2024-10-01DOI: 10.1053/j.seminhematol.2024.08.004
Michelle Choe MD , Corinne Summers MD
Treatment with CD19-targeted chimeric antigen receptor T cell therapy (CD19-CART) has improved salvage rates in children and adults with relapsed and/or refractory B-cell acute lymphoblastic leukemia (ALL). However, not all patients treated with CD19-CAR T cells achieve long-term remission. The role of allogeneic hematopoietic stem cell transplantation as consolidative therapy remains undefined. We aim to review the current literature published to date regarding prognostic markers indicating durable ALL response to CD19-CART and risk factors for relapse after CD19-CART to identify patient cohorts who may benefit from consolidative hematopoietic stem cell transplantation.
CD19 靶向嵌合抗原受体 T 细胞疗法（CD19-CART）提高了复发和/或难治性 B 细胞急性淋巴细胞白血病（ALL）儿童和成人患者的救治率。然而，并非所有接受 CD19-CAR T 细胞治疗的患者都能获得长期缓解。异基因造血干细胞移植作为巩固治疗的作用仍未确定。我们旨在回顾迄今为止发表的有关CD19-CART持久ALL反应预后标志物和CD19-CART后复发风险因素的文献，以确定哪些患者群体可从巩固性造血干细胞移植中获益。
{"title":"The Road More or Less Traveled- Examining the Role of Consolidative Allogeneic Hematopoietic Stem Cell Transplantation After Chimeric Antigen Receptor T Cell Therapy in B-cell ALL","authors":"Michelle Choe MD , Corinne Summers MD","doi":"10.1053/j.seminhematol.2024.08.004","DOIUrl":"10.1053/j.seminhematol.2024.08.004","url":null,"abstract":"<div><div>Treatment with CD19-targeted chimeric antigen receptor T cell therapy (CD19-CART) has improved salvage rates in children and adults with relapsed and/or refractory B-cell acute lymphoblastic leukemia (ALL). However, not all patients treated with CD19-CAR T cells achieve long-term remission. The role of allogeneic hematopoietic stem cell transplantation as consolidative therapy remains undefined. We aim to review the current literature published to date regarding prognostic markers indicating durable ALL response to CD19-CART and risk factors for relapse after CD19-CART to identify patient cohorts who may benefit from consolidative hematopoietic stem cell transplantation.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 5","pages":"Pages 314-320"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381618","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}
Pub Date : 2024-10-01DOI: 10.1053/j.seminhematol.2024.08.002
Kanal Singh , Joseph M. Rocco , Veronique Nussenblatt
Adoptive cellular therapies (ACT) are novel, promising treatments for life-threatening malignancies. In addition to the better known chimeric antigen receptor (CAR) T cells, ACTs include tumor infiltrating lymphocytes (TIL), cancer antigen-specific T cell receptors (TCRs), and CAR-NK (natural killer) cells. In key historic milestones, several adoptive therapies recently received FDA approvals, including 6 CAR-T products for the treatment of hematologic malignancies and the first TIL therapy for the treatment for metastatic melanoma. The rapid pace of clinical trials in the field and the discoveries they provide are ushering in a new era of cancer immunotherapy. However, the potential complications of these therapies are still not fully understood. In particular, patients receiving ACT may be at increased risk for severe infections due to immunocompromise resulting from their underlying malignancies, which are further compounded by the immune derangements that develop in the setting of cellular immunotherapy and/or the preconditioning treatment needed to enhance ACT efficacy. Moreover, these treatments are being readily implemented at a time following the height of the COVID-19 pandemic, and it remains unclear what additional risks these patients may face from SARS-CoV-2 and similar infections. Here, we examine the evidence for infectious complications with emerging adoptive therapies, and provide a focused review of the epidemiology, complications, and clinical management for COVID-19 in CAR-T recipients to understand the risk this disease may pose to recipients of other forms of ACT.
适应性细胞疗法（ACT）是治疗危及生命的恶性肿瘤的新型、有前途的疗法。除了众所周知的嵌合抗原受体（CAR）T 细胞外，ACT 还包括肿瘤浸润淋巴细胞（TIL）、癌症抗原特异性 T 细胞受体（TCR）和 CAR-NK（自然杀伤）细胞。在重要的历史里程碑中，几种采用疗法最近获得了美国食品及药物管理局（FDA）的批准，其中包括 6 种治疗血液恶性肿瘤的 CAR-T 产品和第一种治疗转移性黑色素瘤的 TIL 疗法。该领域临床试验的快速发展及其带来的新发现正在开创癌症免疫疗法的新时代。然而，人们对这些疗法的潜在并发症仍不完全了解。特别是，接受 ACT 治疗的患者可能会因基础恶性肿瘤导致的免疫功能低下而增加严重感染的风险，而细胞免疫疗法和/或提高 ACT 疗效所需的预处理疗法所产生的免疫失调又进一步加剧了这种风险。此外，这些治疗是在 COVID-19 大流行的高峰期后立即实施的，目前仍不清楚这些患者可能面临的 SARS-CoV-2 和类似感染的额外风险。在此，我们研究了新兴收养疗法感染并发症的证据，并重点回顾了CAR-T受者中COVID-19的流行病学、并发症和临床管理，以了解这种疾病可能给其他形式的ACT受者带来的风险。
{"title":"The winding road: Infectious disease considerations for CAR-T and other novel adoptive cellular therapies in the era of COVID-19","authors":"Kanal Singh , Joseph M. Rocco , Veronique Nussenblatt","doi":"10.1053/j.seminhematol.2024.08.002","DOIUrl":"10.1053/j.seminhematol.2024.08.002","url":null,"abstract":"<div><div>Adoptive cellular therapies (ACT) are novel, promising treatments for life-threatening malignancies. In addition to the better known chimeric antigen receptor (CAR) T cells, ACTs include tumor infiltrating lymphocytes (TIL), cancer antigen-specific T cell receptors (TCRs), and CAR-NK (natural killer) cells. In key historic milestones, several adoptive therapies recently received FDA approvals, including 6 CAR-T products for the treatment of hematologic malignancies and the first TIL therapy for the treatment for metastatic melanoma. The rapid pace of clinical trials in the field and the discoveries they provide are ushering in a new era of cancer immunotherapy. However, the potential complications of these therapies are still not fully understood. In particular, patients receiving ACT may be at increased risk for severe infections due to immunocompromise resulting from their underlying malignancies, which are further compounded by the immune derangements that develop in the setting of cellular immunotherapy and/or the preconditioning treatment needed to enhance ACT efficacy. Moreover, these treatments are being readily implemented at a time following the height of the COVID-19 pandemic, and it remains unclear what additional risks these patients may face from SARS-CoV-2 and similar infections. Here, we examine the evidence for infectious complications with emerging adoptive therapies, and provide a focused review of the epidemiology, complications, and clinical management for COVID-19 in CAR-T recipients to understand the risk this disease may pose to recipients of other forms of ACT.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 5","pages":"Pages 321-332"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393079","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}
Pub Date : 2024-10-01DOI: 10.1053/S0037-1963(24)00114-8
{"title":"outside front cover, PMS 8883 metallic AND 4/C","authors":"","doi":"10.1053/S0037-1963(24)00114-8","DOIUrl":"10.1053/S0037-1963(24)00114-8","url":null,"abstract":"","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 5","pages":"Page CO1"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438240","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}
While the advent of CAR-T therapies has heralded a new era of efficacious therapies in relapsed/refractory Multiple Myeloma, access continues to be a major limiting factor due to prolonged manufacturing times of autologous products and apheresis and/or manufacturing failures. Allogeneic adoptive cellular therapy products (CAR-T, CAR-NK), currently investigational, are “off-the-shelf” products that may address availability and manufacturing bottlenecks. Novel rapid manufacturing platforms that decrease adoptive cell therapy product development time by weeks are currently being tested in clinical trials and may additionally help bridge the demand-supply chasm. This review provides a comprehensive overview of allogeneic adoptive cellular therapies and rapid manufacturing platforms in development.
{"title":"Accelerating accessibility of CAR-T/NK therapies – Are AlloCARs and rapid manufacturing platforms the road ahead in improving access in multiple myeloma?","authors":"Sridevi Rajeeve , Abhinav Hoskote , Sham Mailankody","doi":"10.1053/j.seminhematol.2024.09.001","DOIUrl":"10.1053/j.seminhematol.2024.09.001","url":null,"abstract":"<div><div>While the advent of CAR-T therapies has heralded a new era of efficacious therapies in relapsed/refractory Multiple Myeloma, access continues to be a major limiting factor due to prolonged manufacturing times of autologous products and apheresis and/or manufacturing failures. Allogeneic adoptive cellular therapy products (CAR-T, CAR-NK), currently investigational, are “off-the-shelf” products that may address availability and manufacturing bottlenecks. Novel rapid manufacturing platforms that decrease adoptive cell therapy product development time by weeks are currently being tested in clinical trials and may additionally help bridge the demand-supply chasm. This review provides a comprehensive overview of allogeneic adoptive cellular therapies and rapid manufacturing platforms in development.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 5","pages":"Pages 297-305"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381617","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}
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}
Pub Date : 2024-10-01DOI: 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。
{"title":"License for a CAR T: Examining patient eligibility","authors":"Neha Akkad , Dai Chihara","doi":"10.1053/j.seminhematol.2024.07.001","DOIUrl":"10.1053/j.seminhematol.2024.07.001","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 5","pages":"Pages 284-289"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141848180","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号