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Seminars in hematology最新文献

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Modernizing multiple myeloma clinical trial eligibility to improve equity and inclusivity by hematological parameters 多发性骨髓瘤临床试验资格现代化，通过血液学参数提高公平性和包容性。
IF 5 3区 医学
Seminars in hematology Pub Date : 2025-02-01 DOI: 10.1053/j.seminhematol.2024.10.008
Lauren Merz , Monique Hartley-Brown , Maureen Achebe , Craig Cole , Bindu Kanapuru , Ola Banjo , George Mulligan , Katie Wozniak , Anne Quinn Young , Hearn Jay Cho
{"title":"Modernizing multiple myeloma clinical trial eligibility to improve equity and inclusivity by hematological parameters","authors":"Lauren Merz ,&nbsp;Monique Hartley-Brown ,&nbsp;Maureen Achebe ,&nbsp;Craig Cole ,&nbsp;Bindu Kanapuru ,&nbsp;Ola Banjo ,&nbsp;George Mulligan ,&nbsp;Katie Wozniak ,&nbsp;Anne Quinn Young ,&nbsp;Hearn Jay Cho","doi":"10.1053/j.seminhematol.2024.10.008","DOIUrl":"10.1053/j.seminhematol.2024.10.008","url":null,"abstract":"<div><div>In the United States, Black people experience multiple myeloma (MM) at a frequency that is more than double that of White people and experience much higher rates of mortality. Despite bearing a disproportionate impact of both MM incidence and mortality, Black patients are significantly underrepresented in most MM clinical trials. This is in part because Black patients experience a higher prevalence of hemoglobinopathies and Duffy-null phenotype, which affect hemoglobin and neutrophil levels, respectively, potentially excluding patients from clinical trials. The Multiple Myeloma Research Foundation (MMRF) has convened a series of Health Equity Summits that include a focus on creating inclusive clinical trials for MM. The present paper, an output of the most recent workshop, focuses on the role of laboratory reference ranges as a barrier to clinical trial participation and offers tangible steps to improve the enrollment of a diverse and representative population.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"62 1","pages":"Pages 38-42"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710945","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
FaMMily Affairs: Dissecting inherited contributions to multiple myeloma risk 家族事务：剖析遗传因素对多发性骨髓瘤风险的影响。
IF 5 3区 医学
Seminars in hematology Pub Date : 2025-02-01 DOI: 10.1053/j.seminhematol.2024.11.006
Saoirse Bodnar , Tehilla Brander , Julie Gold , Ayuko Iverson , Alessandro Lagana , Kenan Onel , Sundar Jagannath , Samir Parekh , Santiago Thibaud
{"title":"FaMMily Affairs: Dissecting inherited contributions to multiple myeloma risk","authors":"Saoirse Bodnar ,&nbsp;Tehilla Brander ,&nbsp;Julie Gold ,&nbsp;Ayuko Iverson ,&nbsp;Alessandro Lagana ,&nbsp;Kenan Onel ,&nbsp;Sundar Jagannath ,&nbsp;Samir Parekh ,&nbsp;Santiago Thibaud","doi":"10.1053/j.seminhematol.2024.11.006","DOIUrl":"10.1053/j.seminhematol.2024.11.006","url":null,"abstract":"<div><div>Etiological links to multiple myeloma (MM) remain poorly understood, though emerging evidence suggests a significant hereditary component. This review integrates current literature on inherited factors contributing to MM risk, synthesizing both epidemiologic and genomic data. We examine familial clustering patterns, assess genome-wide association studies (GWAS) that reveal common genetic variants linked to MM, and explore rare, high-penetrance variants in key susceptibility genes. Additionally, we advocate for routine germline screening in high-risk MM populations, particularly those with a strong family history of cancer, a personal history of cancer, or early-onset disease. By elucidating the inherited influences on MM predisposition, this review seeks to inform future research and refine risk assessment strategies in this population.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"62 1","pages":"Pages 11-19"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142897072","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
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
Seminars in hematology Pub Date : 2025-02-01 DOI: 10.1053/S0037-1963(25)00004-6
{"title":"outside front cover, PMS 8883 metallic AND 4/C","authors":"","doi":"10.1053/S0037-1963(25)00004-6","DOIUrl":"10.1053/S0037-1963(25)00004-6","url":null,"abstract":"","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"62 1","pages":"Page CO1"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620478","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
At the cusp of a cure in Myeloma: Insights into pathogenesis, modeling and therapeutics
IF 5 3区 医学
Seminars in hematology Pub Date : 2025-02-01 DOI: 10.1053/j.seminhematol.2025.02.002
Samir Parekh MD
{"title":"At the cusp of a cure in Myeloma: Insights into pathogenesis, modeling and therapeutics","authors":"Samir Parekh MD","doi":"10.1053/j.seminhematol.2025.02.002","DOIUrl":"10.1053/j.seminhematol.2025.02.002","url":null,"abstract":"","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"62 1","pages":"Pages 1-2"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620479","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 1q abnormalities in multiple myeloma: Genomic insights, clinical implications, and therapeutic challenges 1q 异常在多发性骨髓瘤中的作用：基因组学见解、临床意义和治疗挑战。
IF 5 3区 医学
Seminars in hematology Pub Date : 2025-02-01 DOI: 10.1053/j.seminhematol.2024.10.001
Zachary M. Avigan , Constantine S. Mitsiades , Alessandro Laganà
{"title":"The role of 1q abnormalities in multiple myeloma: Genomic insights, clinical implications, and therapeutic challenges","authors":"Zachary M. Avigan ,&nbsp;Constantine S. Mitsiades ,&nbsp;Alessandro Laganà","doi":"10.1053/j.seminhematol.2024.10.001","DOIUrl":"10.1053/j.seminhematol.2024.10.001","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"62 1","pages":"Pages 20-30"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","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}
引用次数: 0
Melanoma antigen genes (MAGE); novel functional targets in multiple myeloma 黑色素瘤抗原基因（MAGE）；多发性骨髓瘤的新功能靶点。
IF 5 3区 医学
Seminars in hematology Pub Date : 2025-02-01 DOI: 10.1053/j.seminhematol.2024.10.007
Anna Huo-Chang Mei , Alessandro Laganà , Roman Osman , Hearn Jay Cho
{"title":"Melanoma antigen genes (MAGE); novel functional targets in multiple myeloma","authors":"Anna Huo-Chang Mei ,&nbsp;Alessandro Laganà ,&nbsp;Roman Osman ,&nbsp;Hearn Jay Cho","doi":"10.1053/j.seminhematol.2024.10.007","DOIUrl":"10.1053/j.seminhematol.2024.10.007","url":null,"abstract":"<div><div>Melanoma Antigen Genes (MAGE) are expressed in a broad range of cancers, including multiple myeloma. MAGE have been under investigation for more than 3 decades as targets for immune therapy, while in parallel, interrogation of their functions has revealed activities that may be particularly critical in multiple myeloma. MAGE-C1 is expressed in about 75% of newly diagnosed cases and this is maintained through the natural history of the disease. In contrast, MAGE-A3 is expressed in about 35% of newly diagnosed cases, but this increases to more than 75% after relapse. MAGE-A3 expression was associated with poor clinical outcome and resistance to chemotherapy. Translational studies have revealed that MAGE-A3 regulates cell cycling and apoptosis in myeloma cells. Genomic, gene expression, and multiomic studies demonstrate relations with high-risk subgroups of patients. MAGE-A3 mediates these functions through partnership with Kap1 to form a ubiquitin ligase complex. Structural analysis of the interaction between MAGE-A3 and Kap1 gives insight into the biochemical activity and substrate specificity and suggests novel pharmacologic strategies to inhibit them. These studies demonstrating MAGE-A3 oncogenic functions suggest that it may also be a suitable target for small molecule inhibition in multiple myeloma that may be broadly applicable to other cancers that express it.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"62 1","pages":"Pages 43-49"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695903","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
Smoldering multiple myeloma: Integrating biology and risk into management 燃烧性多发性骨髓瘤：将生物学和风险纳入管理。
IF 5 3区 医学
Seminars in hematology Pub Date : 2025-02-01 DOI: 10.1053/j.seminhematol.2024.10.002
Roshani Patel , Elizabeth Hill , Madhav Dhodapkar
{"title":"Smoldering multiple myeloma: Integrating biology and risk into management","authors":"Roshani Patel ,&nbsp;Elizabeth Hill ,&nbsp;Madhav Dhodapkar","doi":"10.1053/j.seminhematol.2024.10.002","DOIUrl":"10.1053/j.seminhematol.2024.10.002","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"62 1","pages":"Pages 3-10"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","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}
引用次数: 0
Extramedullary myeloma in the era of CAR T-cell and bispecific antibody therapies
IF 5 3区 医学
Seminars in hematology Pub Date : 2025-02-01 DOI: 10.1053/j.seminhematol.2025.02.001
Larysa Sanchez, Shambavi Richard
{"title":"Extramedullary myeloma in the era of CAR T-cell and bispecific antibody therapies","authors":"Larysa Sanchez,&nbsp;Shambavi Richard","doi":"10.1053/j.seminhematol.2025.02.001","DOIUrl":"10.1053/j.seminhematol.2025.02.001","url":null,"abstract":"<div><div>Despite the significant advancements in multiple myeloma therapy over the last decade, current unmet needs include populations of patients who continue to have inferior outcomes, such as those with high-risk cytogenetics, elderly and frail patients, plasma cell leukemia, central nervous system involvement, and extramedullary disease. Though T-cell redirecting therapies have shown excellent efficacy in advanced multiple myeloma, the ability of these therapies to overcome high-risk disease such as extramedullary involvement in myeloma is an area of critical attention. In this review, we seek to examine the specific impact of currently available data of T-cell redirecting therapies, including approved and investigational chimeric antigen receptor T-cell and bispecific antibody therapies, on outcomes in patients with extramedullary myeloma.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"62 1","pages":"Pages 31-37"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531714","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
Immunocompetent mouse models of multiple myeloma 免疫功能正常的多发性骨髓瘤小鼠模型。
IF 5 3区 医学
Seminars in hematology Pub Date : 2025-02-01 DOI: 10.1053/j.seminhematol.2024.11.003
Peter Leif Bergsagel, Marta Chesi
{"title":"Immunocompetent mouse models of multiple myeloma","authors":"Peter Leif Bergsagel,&nbsp;Marta Chesi","doi":"10.1053/j.seminhematol.2024.11.003","DOIUrl":"10.1053/j.seminhematol.2024.11.003","url":null,"abstract":"<div><div>Immunocompetent murine models of multiple myeloma are critical for understanding the pathogenesis of multiple myeloma and for the development of novel immunotherapeutics. Different models are available in Balb/c and C57Bl strains, each with different advantages and disadvantages. The availability of many transplantable cell lines allows for the conduct of experiments with large cohorts of mice bearing identical tumors, while cell lines that grow <em>in vitro</em> can be used for genetic manipulations. The introduction of human <em>CRBN</em> into these models allows for the study of IMiDs and cereblon based PROTACs in mice. New genetically engineered models based on germinal center cell activation of <em>Nsd2</em> or <em>Ccnd1</em> together with constitutive NFkB are being developed to model some of the important genetic subtypes of human multiple myeloma.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"62 1","pages":"Pages 50-57"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824487","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
Advancements in bispecific antibodies for multiple myeloma: What's new and what lies ahead
IF 5 3区 医学
Seminars in hematology Pub Date : 2025-02-01 DOI: 10.1053/j.seminhematol.2024.12.001
Tarek H. Mouhieddine, Bruno Almeida Costa, Joshua Richter
{"title":"Advancements in bispecific antibodies for multiple myeloma: What's new and what lies ahead","authors":"Tarek H. Mouhieddine,&nbsp;Bruno Almeida Costa,&nbsp;Joshua Richter","doi":"10.1053/j.seminhematol.2024.12.001","DOIUrl":"10.1053/j.seminhematol.2024.12.001","url":null,"abstract":"<div><div>Recent advancements in multiple myeloma (MM) treatment—including immunomodulatory drugs, proteasome inhibitors, monoclonal antibodies, and T cell–redirecting therapies like chimeric antigen receptor (CAR) T cells and bispecific antibodies (BsAbs)—have significantly improved patient outcomes. However, MM remains incurable, highlighting the need for novel therapeutic strategies. BsAbs, which simultaneously target a tumor-specific antigen and CD3 on T cells, have shown promising efficacy. Three BsAbs - teclistamab, elranatamab, and talquetamab - have been approved for relapsed or refractory MM, demonstrating response rates of 60 %-74 % and median progression-free survival of approximately 1 year. This review provides a comprehensive overview of the latest advancements in BsAb therapy for MM, focusing on new therapeutic targets such as BCMA, GPRC5D, and FcRH5, recent clinical trial data, safety considerations, and future directions. We discuss tumor-intrinsic mechanisms of resistance, including antigen expression variability and antigen escape, as well as immune-related factors like T-cell exhaustion and an immunosuppressive microenvironment. Future strategies involve integrating BsAbs earlier in treatment, combining them with other agents to enhance efficacy and overcome resistance, and optimizing administration protocols to mitigate adverse effects. By examining these developments, we highlight how BsAbs are reshaping the treatment landscape of MM and underscore the importance of ongoing research to improve survival and quality of life for patients.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"62 1","pages":"Pages 58-70"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067818","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
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