Pub Date : 2024-02-13DOI: 10.1016/j.blre.2024.101182
Thomas M. Kuczmarski , Lizabeth Roemer , Oreofe O. Odejide
Patients with hematologic malignancies experience high rates of depression. These patients are vulnerable to depression throughout the disease trajectory, from diagnosis to survivorship, and at the end of life. In addition to the distressing nature of depression, it has substantial downstream effects including poor quality of life, increased risk of treatment complications, and worse survival. Therefore, systematic screening for depression and integration of robust psychological interventions for affected patients is crucial. Although depression has been historically studied mostly in patients with solid malignancies, research focusing on patients with hematologic malignancies is growing. In this article, we describe what is known about depression in patients with hematologic malignancies, including its assessment, prevalence, risk factors, and implications. We also describe interventions to ameliorate depression in this population. Future research is needed to test effective and scalable interventions to reduce the burden of depression among patients with blood cancers.
{"title":"Depression in patients with hematologic malignancies: The current landscape and future directions","authors":"Thomas M. Kuczmarski , Lizabeth Roemer , Oreofe O. Odejide","doi":"10.1016/j.blre.2024.101182","DOIUrl":"10.1016/j.blre.2024.101182","url":null,"abstract":"<div><p>Patients with hematologic malignancies experience high rates of depression. These patients are vulnerable to depression throughout the disease trajectory, from diagnosis to survivorship, and at the end of life. In addition to the distressing nature of depression, it has substantial downstream effects including poor quality of life, increased risk of treatment complications, and worse survival. Therefore, systematic screening for depression and integration of robust psychological interventions for affected patients is crucial. Although depression has been historically studied mostly in patients with solid malignancies, research focusing on patients with hematologic malignancies is growing. In this article, we describe what is known about depression in patients with hematologic malignancies, including its assessment, prevalence, risk factors, and implications. We also describe interventions to ameliorate depression in this population. Future research is needed to test effective and scalable interventions to reduce the burden of depression among patients with blood cancers.</p></div>","PeriodicalId":56139,"journal":{"name":"Blood Reviews","volume":"65 ","pages":"Article 101182"},"PeriodicalIF":7.4,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139815756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-08DOI: 10.1016/j.blre.2024.101181
Maya Bizri , Rawan Koleilat , Nathalie Akiki , Reem Dergham , Alexandra Monica Mihailescu , Rayan Bou-Fakhredin , Khaled M. Musallam , Ali T. Taher
Advances in understanding the disease process in β-thalassemia supported development of various treatment strategies that resulted in improved survival. Improved survival, however, allowed multiple morbidities to manifest and cemented the need for frequent, lifelong treatment. This has directly impacted patients' health-related quality of life and opened the door for various psychiatric and cognitive disorders to potentially develop. In this review, we summarize available evidence on quality of life, depression and anxiety, suicidality, and cognitive impairment in adult patients with β-thalassemia while sharing our personal insights from experience in treating patients with both transfusion-dependent and non-transfusion-dependent forms.
{"title":"Quality of life, mood disorders, and cognitive impairment in adults with β-thalassemia","authors":"Maya Bizri , Rawan Koleilat , Nathalie Akiki , Reem Dergham , Alexandra Monica Mihailescu , Rayan Bou-Fakhredin , Khaled M. Musallam , Ali T. Taher","doi":"10.1016/j.blre.2024.101181","DOIUrl":"10.1016/j.blre.2024.101181","url":null,"abstract":"<div><p>Advances in understanding the disease process in β-thalassemia supported development of various treatment strategies that resulted in improved survival. Improved survival, however, allowed multiple morbidities to manifest and cemented the need for frequent, lifelong treatment. This has directly impacted patients' health-related quality of life and opened the door for various psychiatric and cognitive disorders to potentially develop. In this review, we summarize available evidence on quality of life, depression and anxiety, suicidality, and cognitive impairment in adult patients with β-thalassemia while sharing our personal insights from experience in treating patients with both transfusion-dependent and non-transfusion-dependent forms.</p></div>","PeriodicalId":56139,"journal":{"name":"Blood Reviews","volume":"65 ","pages":"Article 101181"},"PeriodicalIF":7.4,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139716720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01DOI: 10.1016/j.blre.2024.101180
Malgorzata Mikulska , Chiara Oltolini , Emanuela Zappulo , Michele Bartoletti , Anna Maria Frustaci , Andrea Visentin , Candida Vitale , Francesca R. Mauro
CLL is associated with an increased risk of infectious complications. Treatment with BTK or BCL-2 inhibitors does not seem to increase significantly the risk of opportunistic infections, but the role of combination therapies including BTK and/or BCL-2 inhibitors remains to be established. Various infectious complications can be successfully prevented with appropriate risk management strategies. In this paper we reviewed the international guidelines on prevention and management of infectious complications in patients with CLL treated with BTK or BCL-2 inhibitors. Universal pharmacological anti-herpes, antibacterial or antifungal prophylaxis is not warranted. Reactivation of HBV should be prevented in HBsAg-positive subjects. For HBsAg-negative/HBcAb-positive patients recommendations differ, but in case of combination treatment should follow those for other, particularly anti-CD20, agent. Immunization should be provided preferably before the onset of treatment. Immunoglobulin therapy has favourable impact on morbidity but not mortality in patients with hypogammaglobulinemia and severe or recurrent infections. Lack of high-quality data and heterogeneity of patients or protocols included in the studies might explain differences among the main guidelines. Better data collection is warranted.
{"title":"Prevention and management of infectious complications in patients with chronic lymphocytic leukemia (CLL) treated with BTK and BCL-2 inhibitors, focus on current guidelines","authors":"Malgorzata Mikulska , Chiara Oltolini , Emanuela Zappulo , Michele Bartoletti , Anna Maria Frustaci , Andrea Visentin , Candida Vitale , Francesca R. Mauro","doi":"10.1016/j.blre.2024.101180","DOIUrl":"10.1016/j.blre.2024.101180","url":null,"abstract":"<div><p>CLL is associated with an increased risk of infectious complications. Treatment with BTK or BCL-2 inhibitors does not seem to increase significantly the risk of opportunistic infections, but the role of combination therapies including BTK and/or BCL-2 inhibitors remains to be established. Various infectious complications can be successfully prevented with appropriate risk management strategies. In this paper we reviewed the international guidelines on prevention and management of infectious complications in patients with CLL treated with BTK or BCL-2 inhibitors. Universal pharmacological anti-herpes, antibacterial or antifungal prophylaxis is not warranted. Reactivation of HBV should be prevented in HBsAg-positive subjects. For HBsAg-negative/HBcAb-positive patients recommendations differ, but in case of combination treatment should follow those for other, particularly anti-CD20, agent. Immunization should be provided preferably before the onset of treatment. Immunoglobulin therapy has favourable impact on morbidity but not mortality in patients with hypogammaglobulinemia and severe or recurrent infections. Lack of high-quality data and heterogeneity of patients or protocols included in the studies might explain differences among the main guidelines. Better data collection is warranted.</p></div>","PeriodicalId":56139,"journal":{"name":"Blood Reviews","volume":"65 ","pages":"Article 101180"},"PeriodicalIF":7.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0268960X24000134/pdfft?md5=ddd5ff0f153a77ef736e61e825a3b2c5&pid=1-s2.0-S0268960X24000134-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139670050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-20DOI: 10.1016/j.blre.2024.101172
H. Witte , A. Künstner , N. Gebauer
The vast spectrum of aggressive B-cell non-Hodgkin neoplasms (B-NHL) encompasses several infrequent entities occurring in association with viral infections, posing diagnostic challenges for practitioners. In the emerging era of precision oncology, the molecular characterization of malignancies has acquired paramount significance. The pathophysiological comprehension of specific entities and the identification of targeted therapeutic options have seen rapid development. However, owing to their rarity, not all entities have undergone exhaustive molecular characterization.
Considerable heterogeneity exists in the extant body of work, both in terms of employed methodologies and the scale of cases studied. Presently, therapeutic strategies are predominantly derived from observations in diffuse large B-cell lymphoma (DLBCL), the most prevalent subset of aggressive B-NHL. Ongoing investigations into the molecular profiles of these uncommon virus-associated entities are progressively facilitating a clearer distinction from DLBCL, ultimately paving the way towards individualized therapeutic approaches.
This review consolidates the current molecular insights into aggressive and virus-associated B-NHL, taking into consideration the recently updated 5th edition of the WHO classification of hematolymphoid tumors (WHO-5HAEM) and the International Consensus Classification (ICC). Additionally, potential therapeutically targetable susceptibilities are highlighted, offering a comprehensive overview of the present scientific landscape in the field.
侵袭性 B 细胞非霍奇金肿瘤(B-NHL)的种类繁多,包括几种与病毒感染相关的不常见实体,给从业人员的诊断带来了挑战。在新兴的精准肿瘤学时代,恶性肿瘤的分子特征描述具有极其重要的意义。对特定实体的病理生理学理解和靶向治疗方案的确定得到了快速发展。然而,由于其罕见性,并非所有实体都经过了详尽的分子特征描述。无论从采用的方法还是研究病例的规模来看,现有的研究工作都存在相当大的异质性。目前,治疗策略主要来自对弥漫大 B 细胞淋巴瘤(DLBCL)的观察,这是侵袭性 B-NHL 中最常见的亚群。本综述结合最近更新的第五版世界卫生组织血淋巴肿瘤分类(WHO-5HAEM)和国际共识分类(ICC),综述了目前对侵袭性和病毒相关 B-NHL 的分子研究。此外,还强调了潜在的治疗靶点易感性,全面概述了该领域目前的科学状况。
{"title":"Update: The molecular spectrum of virus-associated high-grade B-cell non-Hodgkin lymphomas","authors":"H. Witte , A. Künstner , N. Gebauer","doi":"10.1016/j.blre.2024.101172","DOIUrl":"10.1016/j.blre.2024.101172","url":null,"abstract":"<div><p>The vast spectrum of aggressive B-cell non-Hodgkin neoplasms (B-NHL) encompasses several infrequent entities occurring in association with viral infections, posing diagnostic challenges for practitioners. In the emerging era of precision oncology, the molecular characterization of malignancies has acquired paramount significance. The pathophysiological comprehension of specific entities and the identification of targeted therapeutic options have seen rapid development. However, owing to their rarity, not all entities have undergone exhaustive molecular characterization.</p><p>Considerable heterogeneity exists in the extant body of work, both in terms of employed methodologies and the scale of cases studied. Presently, therapeutic strategies are predominantly derived from observations in diffuse large B-cell lymphoma (DLBCL), the most prevalent subset of aggressive B-NHL. Ongoing investigations into the molecular profiles of these uncommon virus-associated entities are progressively facilitating a clearer distinction from DLBCL, ultimately paving the way towards individualized therapeutic approaches.</p><p>This review consolidates the current molecular insights into aggressive and virus-associated B-NHL, taking into consideration the recently updated 5th edition of the WHO classification of hematolymphoid tumors (WHO-5HAEM) and the International Consensus Classification (ICC). Additionally, potential therapeutically targetable susceptibilities are highlighted, offering a comprehensive overview of the present scientific landscape in the field.</p></div>","PeriodicalId":56139,"journal":{"name":"Blood Reviews","volume":"65 ","pages":"Article 101172"},"PeriodicalIF":7.4,"publicationDate":"2024-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0268960X24000055/pdfft?md5=b6fed54c1013340b4eafb52f8bc52263&pid=1-s2.0-S0268960X24000055-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139509835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anticoagulation therapy (AT) is fundamental in atrial fibrillation (AF) treatment but poses challenges in implementation, especially in AF populations with elevated thromboembolic and bleeding risks. Current guidelines emphasize the need to estimate and balance thrombosis and bleeding risks for all potential candidates of antithrombotic therapy. However, administering oral AT raises concerns in specific populations, such as those with chronic kidney disease (CKD), coagulation disorders, and cancer due to lack of robust data. These groups, excluded from large direct oral anticoagulants trials, rely on observational studies, prompting physicians to adopt individualized management strategies based on case-specific evaluations. The scarcity of evidence and specific guidelines underline the need for a tailored approach, emphasizing regular reassessment of risk factors and anticoagulation drug doses. This narrative review aims to summarize evidence and recommendations for challenging AF clinical scenarios, particularly in the long-term management of AT for patients with CKD, coagulation disorders, and cancer.
{"title":"When anticoagulation management in atrial fibrillation becomes difficult: Focus on chronic kidney disease, coagulation disorders, and cancer","authors":"Panteleimon E. Papakonstantinou , Vasiliki Kalogera , Dimitrios Charitos , Dimitrios Polyzos , Dimitra Benia , Athina Batsouli , Konstantinos Lampropoulos , Sotirios Xydonas , Dhiraj Gupta , Gregory Y.H. Lip","doi":"10.1016/j.blre.2024.101171","DOIUrl":"10.1016/j.blre.2024.101171","url":null,"abstract":"<div><p>Anticoagulation<span><span> therapy (AT) is fundamental in atrial fibrillation<span><span> (AF) treatment but poses challenges in implementation, especially in AF populations with elevated </span>thromboembolic and bleeding risks. Current guidelines emphasize the need to estimate and balance thrombosis and bleeding risks for all potential candidates of </span></span>antithrombotic therapy<span><span>. However, administering oral AT raises concerns in specific populations, such as those with chronic kidney disease (CKD), </span>coagulation disorders<span><span>, and cancer due to lack of robust data. These groups, excluded from large direct oral anticoagulants trials, rely on observational studies, prompting physicians to adopt individualized management strategies based on case-specific evaluations. The scarcity of evidence and specific guidelines underline the need for a tailored approach, emphasizing regular reassessment of risk factors and </span>anticoagulation drug doses. This narrative review aims to summarize evidence and recommendations for challenging AF clinical scenarios, particularly in the long-term management of AT for patients with CKD, coagulation disorders, and cancer.</span></span></span></p></div>","PeriodicalId":56139,"journal":{"name":"Blood Reviews","volume":"65 ","pages":"Article 101171"},"PeriodicalIF":7.4,"publicationDate":"2024-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139469408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-14DOI: 10.1016/j.blre.2024.101170
Susan K. Parsons , Angie Mae Rodday , Jenica N. Upshaw , Carlton D. Scharman , Zhu Cui , Yenong Cao , Yun Kyoung Ryu Tiger , Matthew J. Maurer , Andrew M. Evens
Hodgkin lymphoma is a rare, but highly curative form of cancer, primarily afflicting adolescents and young adults. Despite multiple seminal trials over the past twenty years, there is no single consensus-based treatment approach beyond use of multi-agency chemotherapy with curative intent. The use of radiation continues to be debated in early-stage disease, as part of combined modality treatment, as well as in salvage, as an important form of consolidation. While short-term disease outcomes have varied little across these different approaches across both early and advanced stage disease, the potential risk of severe, longer-term risk has varied considerably.
Over the past decade novel therapeutics have been employed in the retrieval setting in preparation to and as consolidation after autologous stem cell transplant. More recently, these novel therapeutics have moved to the frontline setting, initially compared to standard-of-care treatment and later in a direct head-to-head comparison combined with multi-agent chemotherapy.
In 2018, we established the HoLISTIC Consortium, bringing together disease and methods experts to develop clinical decision models based on individual patient data to guide providers, patients, and caregivers in decision-making. In this review, we detail the steps we followed to create the master database of individual patient data from patients treated over the past 20 years, using principles of data science. We then describe different methodological approaches we are taking to clinical decision making, beginning with clinical prediction tools at the time of diagnosis, to multi-state models, incorporating treatments and their response. Finally, we describe how simulation modeling can be used to estimate risks of late effects, based on cumulative exposure from frontline and salvage treatment.
The resultant database and tools employed are dynamic with the expectation that they will be updated as better and more complete information becomes available.
{"title":"Harnessing multi-source data for individualized care in Hodgkin Lymphoma","authors":"Susan K. Parsons , Angie Mae Rodday , Jenica N. Upshaw , Carlton D. Scharman , Zhu Cui , Yenong Cao , Yun Kyoung Ryu Tiger , Matthew J. Maurer , Andrew M. Evens","doi":"10.1016/j.blre.2024.101170","DOIUrl":"10.1016/j.blre.2024.101170","url":null,"abstract":"<div><p><span>Hodgkin lymphoma is a rare, but highly curative form of cancer, primarily afflicting adolescents and young adults. Despite multiple seminal trials over the past twenty years, there is no single consensus-based </span>treatment approach beyond use of multi-agency chemotherapy with curative intent. The use of radiation continues to be debated in early-stage disease, as part of combined modality treatment, as well as in salvage, as an important form of consolidation. While short-term disease outcomes have varied little across these different approaches across both early and advanced stage disease, the potential risk of severe, longer-term risk has varied considerably.</p><p>Over the past decade novel therapeutics have been employed in the retrieval setting in preparation to and as consolidation after autologous stem cell transplant. More recently, these novel therapeutics have moved to the frontline setting, initially compared to standard-of-care treatment and later in a direct head-to-head comparison combined with multi-agent chemotherapy.</p><p><span>In 2018, we established the HoLISTIC Consortium, bringing together disease and methods experts to develop clinical decision models based on individual patient data to guide providers, patients, and caregivers in decision-making. In this review, we detail the steps we followed to create the master database of individual patient data from patients treated over the past 20 years, using principles of data science. We then describe different methodological approaches we are taking to clinical decision making, beginning with clinical prediction tools at the time of diagnosis, to multi-state models, incorporating treatments and their response. Finally, we describe how simulation modeling can be used to </span><em>estimate</em> risks of late effects, based on cumulative exposure from frontline and salvage treatment.</p><p>The resultant database and tools employed are <em>dynamic</em> with the expectation that they will be updated as better and more complete information becomes available.</p></div>","PeriodicalId":56139,"journal":{"name":"Blood Reviews","volume":"65 ","pages":"Article 101170"},"PeriodicalIF":7.4,"publicationDate":"2024-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139464046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-08DOI: 10.1016/j.blre.2024.101169
Xiaoyi Chen , Mihir Shukla , Shella Saint Fleur-Lominy
In the recent few decades, outcomes in patients diagnosed with hematological malignancies have been steadily improving. However, the improved prognosis does not distribute equally among patients from different backgrounds. Besides cancer biology, demographic and geographic disparities have been found to impact overall survival significantly. Specifically, patients from underrepresented minorities including Black and Hispanics, and those with uninsured status, having low socioeconomic status, or from rural areas have had worse outcomes historically, which is uniformly true across all major subtypes of hematological malignancies. Similar discrepancy is also seen in the health care professional field, where a gender gap and a disproportionally low representation of health care providers from underrepresented minorities have been long existing. Thus, a comprehensive strategy to mitigate disparity in the health care system is needed to achieve equity in health care.
{"title":"Disparity in hematological malignancies: From patients to health care professionals","authors":"Xiaoyi Chen , Mihir Shukla , Shella Saint Fleur-Lominy","doi":"10.1016/j.blre.2024.101169","DOIUrl":"10.1016/j.blre.2024.101169","url":null,"abstract":"<div><p><span><span>In the recent few decades, outcomes in patients diagnosed with </span>hematological malignancies<span> have been steadily improving. However, the improved prognosis does not distribute equally among patients from different backgrounds. Besides cancer biology, demographic and geographic disparities have been found to impact </span></span>overall survival<span> significantly. Specifically, patients from underrepresented minorities including Black and Hispanics, and those with uninsured status, having low socioeconomic status, or from rural areas have had worse outcomes historically, which is uniformly true across all major subtypes of hematological malignancies. Similar discrepancy is also seen in the health care professional field, where a gender gap and a disproportionally low representation of health care providers from underrepresented minorities have been long existing. Thus, a comprehensive strategy to mitigate disparity in the health care system is needed to achieve equity in health care.</span></p></div>","PeriodicalId":56139,"journal":{"name":"Blood Reviews","volume":"65 ","pages":"Article 101169"},"PeriodicalIF":7.4,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139412089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.1016/j.blre.2023.101140
Taylor R. Brooks , Paolo F. Caimi
The available treatments for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) have experienced a dramatic change since 2017. Incremental advances in basic and translational science over several decades have led to innovations in immune-oncology. These innovations have culminated in eight separate approvals by the US Food and Drug Administration for the treatment of patients with R/R DLBCL over the last 10 years. High-dose therapy and autologous stem cell transplant (HDT-ASCT) remains the standard of care for transplant-eligible patients who relapse after an initial remission. For transplant-ineligible patients or for those who relapse following HDT-ASCT, multiple options exist. Monoclonal antibodies targeting CD19, antibody-drug conjugates, bispecific antibodies, immune effector cell products, and other agents with novel mechanisms of action are now available for patients with R/R DLBCL. There is increasing use of chimeric antigen receptor (CAR) T-cells as second-line therapy for patients with early relapse of DLBCL or those who are refractory to initial chemoimmunotherapy. The clinical benefits of these strategies vary and are influenced by patient and disease characteristics, as well as the type of prior therapy administered. Therefore, there are multiple clinical scenarios that clinicians might encounter when treating R/R DLBCL. An optimal sequence of drugs has not been established, and there is no evidence-based consensus on how to best order these agents. This abundance of choices introduces a paradox: proliferating treatment options are initially a boon to patients and providers, but as choices grow further they no longer liberate. Rather, more choices make the management of R/R DLBCL more challenging due to lack of direct comparisons among agents and a desire to maximize patient outcomes. Here, we provide a review of recently-approved second- and subsequent-line agents, summarize real-world data detailing the use of these medicines, and provide a framework for sequencing therapy in R/R DLBCL.
{"title":"A paradox of choice: Sequencing therapy in relapsed/refractory diffuse large B-cell lymphoma","authors":"Taylor R. Brooks , Paolo F. Caimi","doi":"10.1016/j.blre.2023.101140","DOIUrl":"10.1016/j.blre.2023.101140","url":null,"abstract":"<div><p>The available treatments for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) have experienced a dramatic change since 2017. Incremental advances in basic and translational science over several decades have led to innovations in immune-oncology. These innovations have culminated in eight separate approvals by the US Food and Drug Administration for the treatment of patients with R/R DLBCL over the last 10 years. High-dose therapy and autologous stem cell transplant (HDT-ASCT) remains the standard of care for transplant-eligible patients who relapse after an initial remission. For transplant-ineligible patients or for those who relapse following HDT-ASCT, multiple options exist. Monoclonal antibodies targeting CD19, antibody-drug conjugates, bispecific antibodies, immune effector cell products, and other agents with novel mechanisms of action are now available for patients with R/R DLBCL. There is increasing use of chimeric antigen receptor (CAR) T-cells as second-line therapy for patients with early relapse of DLBCL or those who are refractory to initial chemoimmunotherapy. The clinical benefits of these strategies vary and are influenced by patient and disease characteristics, as well as the type of prior therapy administered. Therefore, there are multiple clinical scenarios that clinicians might encounter when treating R/R DLBCL. An optimal sequence of drugs has not been established, and there is no evidence-based consensus on how to best order these agents. This abundance of choices introduces a paradox: proliferating treatment options are initially a boon to patients and providers, but as choices grow further they no longer liberate. Rather, more choices make the management of R/R DLBCL more challenging due to lack of direct comparisons among agents and a desire to maximize patient outcomes. Here, we provide a review of recently-approved second- and subsequent-line agents, summarize real-world data detailing the use of these medicines, and provide a framework for sequencing therapy in R/R DLBCL.</p></div>","PeriodicalId":56139,"journal":{"name":"Blood Reviews","volume":"63 ","pages":"Article 101140"},"PeriodicalIF":7.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0268960X23001017/pdfft?md5=017ece5e4ab2e983af224f8bb953f889&pid=1-s2.0-S0268960X23001017-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72212076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.1016/j.blre.2023.101138
Amal El-Beshlawy , Hany Dewedar , Salwa Hindawi , Salam Alkindi , Azza A. Tantawy , Mohamed A. Yassin , Ali T. Taher
β-Thalassemia is one of the most common monogenetic diseases worldwide, with a particularly high prevalence in the Middle East region. As such, we have developed long-standing experience with disease management and devising solutions to address challenges attributed to resource limitations. The region has also participated in the majority of clinical trials and development programs of iron chelators and more novel ineffective erythropoiesis-targeted therapy. In this review, we provide a practical overview of management for patients with transfusion-dependent β-thalassemia, primarily driven by such experiences, with the aim of transferring knowledge to colleagues in other regions facing similar challenges.
{"title":"Management of transfusion-dependent β-thalassemia (TDT): Expert insights and practical overview from the Middle East","authors":"Amal El-Beshlawy , Hany Dewedar , Salwa Hindawi , Salam Alkindi , Azza A. Tantawy , Mohamed A. Yassin , Ali T. Taher","doi":"10.1016/j.blre.2023.101138","DOIUrl":"10.1016/j.blre.2023.101138","url":null,"abstract":"<div><p>β-Thalassemia is one of the most common monogenetic diseases worldwide, with a particularly high prevalence in the Middle East region. As such, we have developed long-standing experience with disease management and devising solutions to address challenges attributed to resource limitations. The region has also participated in the majority of clinical trials and development programs of iron chelators and more novel ineffective erythropoiesis-targeted therapy. In this review, we provide a practical overview of management for patients with transfusion-dependent β-thalassemia, primarily driven by such experiences, with the aim of transferring knowledge to colleagues in other regions facing similar challenges.</p></div>","PeriodicalId":56139,"journal":{"name":"Blood Reviews","volume":"63 ","pages":"Article 101138"},"PeriodicalIF":7.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0268960X23000991/pdfft?md5=bbdd1ac89881b56132dc0258a258a5f4&pid=1-s2.0-S0268960X23000991-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49694303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.1016/j.blre.2023.101142
Hanaa Fatoum , Robert Zeiser , Shahrukh K. Hashmi
Chronic graft-versus-host-disease (cGvHD) remains the leading cause of morbidity among transplant recipients. The efficacy of second-line treatments varies widely based on many factors, including wide differences in the organ overall response-rate response and in the current era where multiple agents are approved, and optimal sequencing of drugs based on organ ORR is unknown. We aimed to evaluate outcomes based on ORRs to the most common agents for the treatment of steroid-refractory/steroid-dependent cGvHD by conducting a systematic literature review. A total of 387 studies were evaluated for the ORRs of 12 cGvHD treatments. The highest skin ORR was observed to be 77% though some agents had an acceptable ORR. Most agents had an ocular response ranging from 17 to 50% Some agents resulted in a GI ORR of ≥88%. Rituximab showed the best response for musculoskeletal-GvHD. In the case of lung-GvHD (bronchiolitis obliterans syndrome [BOS]), negligible response was observed in patients treated with various agents. No clinically meaningful responses to treatments were reported for genital-GvHD. Most GvHD trials are focused on the ORR and partial response rates (PRR). The evidence for optimal agents for each organ is limited, and therefore, our study results are striking for differences in organ-ORR yields for a clinically meaningful difference. Thus, a personalized organ-based approach to the selection of therapeutic agents in cGvHD could result in favorable outcomes.
{"title":"A personalized, organ-based approach to the treatment of chronic steroid-refractory graft-versus-host disease","authors":"Hanaa Fatoum , Robert Zeiser , Shahrukh K. Hashmi","doi":"10.1016/j.blre.2023.101142","DOIUrl":"10.1016/j.blre.2023.101142","url":null,"abstract":"<div><p>Chronic graft-versus-host-disease (cGvHD) remains the leading cause of morbidity among transplant recipients. The efficacy of second-line treatments varies widely based on many factors, including wide differences in the organ overall response-rate response and in the current era where multiple agents are approved, and optimal sequencing of drugs based on organ ORR is unknown. We aimed to evaluate outcomes based on ORRs to the most common agents for the treatment of steroid-refractory/steroid-dependent cGvHD by conducting a systematic literature review. A total of 387 studies were evaluated for the ORRs of 12 cGvHD treatments. The highest skin ORR was observed to be 77% though some agents had an acceptable ORR. Most agents had an ocular response ranging from 17 to 50% Some agents resulted in a GI ORR of ≥88%. Rituximab showed the best response for musculoskeletal-GvHD. In the case of lung-GvHD (bronchiolitis obliterans syndrome [BOS]), negligible response was observed in patients treated with various agents. No clinically meaningful responses to treatments were reported for genital-GvHD. Most GvHD trials are focused on the ORR and partial response rates (PRR). The evidence for optimal agents for each organ is limited, and therefore, our study results are striking for differences in organ-ORR yields for a clinically meaningful difference. Thus, a personalized organ-based approach to the selection of therapeutic agents in cGvHD could result in favorable outcomes.</p></div>","PeriodicalId":56139,"journal":{"name":"Blood Reviews","volume":"63 ","pages":"Article 101142"},"PeriodicalIF":7.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0268960X23001030/pdfft?md5=f71104c627612e349c961bc6377df227&pid=1-s2.0-S0268960X23001030-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135671432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}