Pub Date : 2025-02-20DOI: 10.1016/j.blre.2025.101273
Xin Liu , Yufan Lin , Qiqi Zhuang , Haoren Deng , Aichun Liu , Jie Sun
Bruton tyrosine kinase inhibitors (BTKi) have shown prominent clinical efficacy in patients with B cell malignancies, such as chronic lymphocytic leukemia, mantle cell lymphoma, diffuse large B cell lymphoma, and Waldenström's macroglobulinemia. Nevertheless, numerous factors contribute to BTKi resistance, encompassing genetic mutations, chromosomal aberrations, dysregulation of protein expression, tumor microenvironment, and metabolic reprogramming. Accordingly, potential therapeutic strategies have been explored to surmount BTKi resistance, including noncovalent BTKi, BTK proteolysis-targeting chimeras, and combination therapies. Herein, we summarize the mechanisms responsible for BTKi resistance as well as the current preclinical and clinical strategies to address BTKi resistance in B cell malignancies treatment.
{"title":"BTK inhibitors resistance in B cell malignancies: Mechanisms and potential therapeutic strategies","authors":"Xin Liu , Yufan Lin , Qiqi Zhuang , Haoren Deng , Aichun Liu , Jie Sun","doi":"10.1016/j.blre.2025.101273","DOIUrl":"10.1016/j.blre.2025.101273","url":null,"abstract":"<div><div>Bruton tyrosine kinase inhibitors (BTKi) have shown prominent clinical efficacy in patients with B cell malignancies, such as chronic lymphocytic leukemia, mantle cell lymphoma, diffuse large B cell lymphoma, and Waldenström's macroglobulinemia. Nevertheless, numerous factors contribute to BTKi resistance, encompassing genetic mutations, chromosomal aberrations, dysregulation of protein expression, tumor microenvironment, and metabolic reprogramming. Accordingly, potential therapeutic strategies have been explored to surmount BTKi resistance, including noncovalent BTKi, BTK proteolysis-targeting chimeras, and combination therapies. Herein, we summarize the mechanisms responsible for BTKi resistance as well as the current preclinical and clinical strategies to address BTKi resistance in B cell malignancies treatment.</div></div>","PeriodicalId":56139,"journal":{"name":"Blood Reviews","volume":"71 ","pages":"Article 101273"},"PeriodicalIF":6.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506308","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 : 2025-02-15DOI: 10.1016/j.blre.2025.101272
Simona Pagliuca , Florent Malard , Jarl E. Mooyaart , Michael Daskalakis , Ludovic Gabellier , Ibrahim Yakoub-Agha , Ron Ram , Caroline Besley , Edouard Forcade , Vladan Vucinic , Lucía López Corral , Jan Vydra , Bastian von Tresckow , Paula Amat , Persis Amrolia , Peter Vandenberghe , Friedrich Stölzel , Simona Sica , Marie Thérèse Rubio , Jorinde D. Hoogenboom , Annalisa Ruggeri
Immune monitoring of cell therapies is a complex and evolving topic, particularly in the rapid expanding field of chimeric antigen receptor T (CAR-T) cell applications. Defining essential, recommended, and optional immune monitoring data post-CAR-T cell infusion is crucial to improve patient outcomes and inform post-treatment decisions. To address this gap, we conducted a survey-based study across centers affiliated with the European Society for Blood and Marrow Transplantation (EBMT), focusing on patients treated with European Medicines Agency (EMA)-approved CAR-T products. Building on a thorough review of the literature, we mapped the current landscape of immune monitoring practices and assessed their impact on clinical management. By defining the state of the art in the field, this work marks an initial step towards a structured harmonization process potentially able to enhance the management and outcomes of patients undergoing these immune cell therapies.
{"title":"The landscape of immune monitoring in CAR-T cell therapy: A comprehensive review and survey study by the Cellular Therapy and Immunobiology Working Party of the EBMT","authors":"Simona Pagliuca , Florent Malard , Jarl E. Mooyaart , Michael Daskalakis , Ludovic Gabellier , Ibrahim Yakoub-Agha , Ron Ram , Caroline Besley , Edouard Forcade , Vladan Vucinic , Lucía López Corral , Jan Vydra , Bastian von Tresckow , Paula Amat , Persis Amrolia , Peter Vandenberghe , Friedrich Stölzel , Simona Sica , Marie Thérèse Rubio , Jorinde D. Hoogenboom , Annalisa Ruggeri","doi":"10.1016/j.blre.2025.101272","DOIUrl":"10.1016/j.blre.2025.101272","url":null,"abstract":"<div><div>Immune monitoring of cell therapies is a complex and evolving topic, particularly in the rapid expanding field of chimeric antigen receptor T (CAR-T) cell applications. Defining essential, recommended, and optional immune monitoring data post-CAR-T cell infusion is crucial to improve patient outcomes and inform post-treatment decisions. To address this gap, we conducted a survey-based study across centers affiliated with the European Society for Blood and Marrow Transplantation (EBMT), focusing on patients treated with European Medicines Agency (EMA)-approved CAR-T products. Building on a thorough review of the literature, we mapped the current landscape of immune monitoring practices and assessed their impact on clinical management. By defining the state of the art in the field, this work marks an initial step towards a structured harmonization process potentially able to enhance the management and outcomes of patients undergoing these immune cell therapies.</div></div>","PeriodicalId":56139,"journal":{"name":"Blood Reviews","volume":"71 ","pages":"Article 101272"},"PeriodicalIF":6.9,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477287","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}
Classic Hodgkin lymphoma (cHL) is defined by distinctive Hodgkin Reed-Sternberg (HRS) cells, which are CD30+/CD15+ multinucleated tumor cells lacking typical B-cell markers. These cells comprise <5 % of tumor mass but orchestrate an extensive immunosuppressive tumor microenvironment (TME). Classic HL was curable with radiation therapy and multi-agent chemotherapy. Despite high cure rates, treatment-related toxicities remain significant. The goals of multimodality therapy are to achieve a cure while minimizing treatment-associated toxicity. Advances in molecular insights into HRS cells have led to transformative therapies, including checkpoint inhibitors, antibody-drug conjugates like brentuximab vedotin, which have shown remarkable efficacy, especially in relapsed or refractory disease. However, challenges persist due to the heterogeneity of cHL, driven by the complex biology of HRS cells and their surrounding tumor microenvironment. Novel approaches such as single-cell RNA sequencing and circulating tumor DNA profiling provide promising strategies to address these challenges. This review examines the origin, morphology, phenotype, and genetic profiles of HRS cells, highlighting key pathobiological features, including biomarkers and Epstein-Barr Virus involvement. It also explores the biological mechanisms underlying HRS cell survival and evaluates standard and emerging therapies, offering insights into the rationale for novel treatment strategies.
典型霍奇金淋巴瘤（cHL）由独特的霍奇金里德-斯登堡（HRS）细胞定义，这些细胞是 CD30+/CD15+ 多核肿瘤细胞，缺乏典型的 B 细胞标记。这些细胞包括
{"title":"Classic Hodgkin lymphoma: Pathobiological features that impact emerging therapies","authors":"Mohamed Nazem Alibrahim , Annunziata Gloghini , Antonino Carbone","doi":"10.1016/j.blre.2025.101271","DOIUrl":"10.1016/j.blre.2025.101271","url":null,"abstract":"<div><div>Classic Hodgkin lymphoma (cHL) is defined by distinctive Hodgkin Reed-Sternberg (HRS) cells, which are CD30+/CD15+ multinucleated tumor cells lacking typical B-cell markers. These cells comprise <5 % of tumor mass but orchestrate an extensive immunosuppressive tumor microenvironment (TME). Classic HL was curable with radiation therapy and multi-agent chemotherapy. Despite high cure rates, treatment-related toxicities remain significant. The goals of multimodality therapy are to achieve a cure while minimizing treatment-associated toxicity. Advances in molecular insights into HRS cells have led to transformative therapies, including checkpoint inhibitors, antibody-drug conjugates like brentuximab vedotin, which have shown remarkable efficacy, especially in relapsed or refractory disease. However, challenges persist due to the heterogeneity of cHL, driven by the complex biology of HRS cells and their surrounding tumor microenvironment. Novel approaches such as single-cell RNA sequencing and circulating tumor DNA profiling provide promising strategies to address these challenges. This review examines the origin, morphology, phenotype, and genetic profiles of HRS cells, highlighting key pathobiological features, including biomarkers and Epstein-Barr Virus involvement. It also explores the biological mechanisms underlying HRS cell survival and evaluates standard and emerging therapies, offering insights into the rationale for novel treatment strategies.</div></div>","PeriodicalId":56139,"journal":{"name":"Blood Reviews","volume":"71 ","pages":"Article 101271"},"PeriodicalIF":6.9,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191489","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 : 2025-01-28DOI: 10.1016/j.blre.2025.101270
Marc Sorigue , Milos Miljkovic , Pablo Mozas
The strength of evidence supporting use of PET in the evaluation of suspected histological transformation (HT) of follicular lymphoma (FL) is unknown. We conducted a systematic review of studies reporting the diagnostic performance of ≥1 PET parameters for the detection of HT in patients with known FL. We searched PubMed for any study reporting ≥1 diagnostic performance metrics. Risk of bias was evaluated with the QUADAS2 tool. We included 7 studies encompassing 152 patients with a biopsy showing FL (or indolent non-Hodgkin lymphoma) and 111 with a biopsy confirming HT. Study designs and study populations differed substantially. PET methods were poorly reported and 18F-FDG dose was highly variable. Most studies were judged to be at high risk of bias in the patient and index test domains of QUADAS2. The diagnostic performance of 5 PET parameters were reported in at least one study but only SUVmax (n = 7) was reported in >2. Median SUVmax ranged from 9.2 to 10.9 in FL/iNHL and from 13.7 to 24.4 in HT. While SUVmax was consistently higher in the HT group, there was considerable overlap between the two groups and significant variability between studies. Area under the ROC curve for SUVmax to distinguish between FL/iNHL and HT ranged from 0.68 to 0.97. Sensitivity and specificity of the proposed cutoffs also varied widely (sensitivity ∼0.6 to 1, specificity ∼0.4 to 1). In conclusion, few studies — mostly small and potentially biased — have addressed this question. Although SUVmax is generally higher in HT than in FL, the diagnostic performance and optimal cutoffs remain unclear. Proposed SUVmax cutoffs should not be used to determine whether a patient has HT or to decide whether a biopsy should be obtained. For now, we encourage physicians to evaluate results of their own practice to devise a prudent workup of suspected.
{"title":"PET scan for the detection of histological transformation of follicular lymphoma: A systematic review of diagnostic performance","authors":"Marc Sorigue , Milos Miljkovic , Pablo Mozas","doi":"10.1016/j.blre.2025.101270","DOIUrl":"10.1016/j.blre.2025.101270","url":null,"abstract":"<div><div>The strength of evidence supporting use of PET in the evaluation of suspected histological transformation (HT) of follicular lymphoma (FL) is unknown. We conducted a systematic review of studies reporting the diagnostic performance of ≥1 PET parameters for the detection of HT in patients with known FL. We searched PubMed for any study reporting ≥1 diagnostic performance metrics. Risk of bias was evaluated with the QUADAS2 tool. We included 7 studies encompassing 152 patients with a biopsy showing FL (or indolent non-Hodgkin lymphoma) and 111 with a biopsy confirming HT. Study designs and study populations differed substantially. PET methods were poorly reported and <sup>18</sup>F-FDG dose was highly variable. Most studies were judged to be at high risk of bias in the patient and index test domains of QUADAS2. The diagnostic performance of 5 PET parameters were reported in at least one study but only SUVmax (<em>n</em> = 7) was reported in >2. Median SUVmax ranged from 9.2 to 10.9 in FL/iNHL and from 13.7 to 24.4 in HT. While SUVmax was consistently higher in the HT group, there was considerable overlap between the two groups and significant variability between studies. Area under the ROC curve for SUVmax to distinguish between FL/iNHL and HT ranged from 0.68 to 0.97. Sensitivity and specificity of the proposed cutoffs also varied widely (sensitivity ∼0.6 to 1, specificity ∼0.4 to 1). In conclusion, few studies — mostly small and potentially biased — have addressed this question. Although SUVmax is generally higher in HT than in FL, the diagnostic performance and optimal cutoffs remain unclear. Proposed SUVmax cutoffs should not be used to determine whether a patient has HT or to decide whether a biopsy should be obtained. For now, we encourage physicians to evaluate results of their own practice to devise a prudent workup of suspected.</div></div>","PeriodicalId":56139,"journal":{"name":"Blood Reviews","volume":"71 ","pages":"Article 101270"},"PeriodicalIF":6.9,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076404","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}
Targeted therapies, consisting of Bruton tyrosine kinase inhibitors (BTKis) or BCL-2 inhibitors, are the mainstay of contemporary treatments for chronic lymphocytic leukemia (CLL). The most common adverse effects (AEs) of BTKis are fatigue, bruising, infection, hematological and cardiovascular AEs. While AEs during treatment are usually mild (grades 1 and 2), grade 3 and 4 AEs have been detected in some patients, necessitating additional medical care and temporary or permanent drug discontinuation. In this review, we analyzed the cardiovascular effects associated with BTKi therapy for CLL and the essential practical aspects of multidisciplinary management of patients who develop cardiovascular toxicity during treatment. We particularly focus on the data and strategies for controlling cardiovascular risks associated with ibrutinib and newer BTKis (acalabrutinib, zanubrutinib and pirtobrutinib), including the development of atrial fibrillation, hypertension, ventricular arrhythmias, sudden death, heart failure, bleeding, and ischemic complications (stroke and myocardial infarction). This review highlights hematological insights underlying cardiotoxicity, an area that has received limited attention in comparison to the predominantly cardiological perspective. This review synthesizes emerging evidence on hematological biomarkers, cardiotoxic mechanisms, and therapeutic interventions, linking hematology and cardiology to enhance understanding and guide comprehensive prevention and management strategies.
{"title":"BTKi-induced cardiovascular toxicity in CLL: Risk mitigation and management strategies","authors":"Sofija Kozarac , Vojin Vukovic , Michael Fradley , Darko Antic","doi":"10.1016/j.blre.2025.101268","DOIUrl":"10.1016/j.blre.2025.101268","url":null,"abstract":"<div><div>Targeted therapies, consisting of Bruton tyrosine kinase inhibitors (BTKis) or BCL-2 inhibitors, are the mainstay of contemporary treatments for chronic lymphocytic leukemia (CLL). The most common adverse effects (AEs) of BTKis are fatigue, bruising, infection, hematological and cardiovascular AEs. While AEs during treatment are usually mild (grades 1 and 2), grade 3 and 4 AEs have been detected in some patients, necessitating additional medical care and temporary or permanent drug discontinuation. In this review, we analyzed the cardiovascular effects associated with BTKi therapy for CLL and the essential practical aspects of multidisciplinary management of patients who develop cardiovascular toxicity during treatment. We particularly focus on the data and strategies for controlling cardiovascular risks associated with ibrutinib and newer BTKis (acalabrutinib, zanubrutinib and pirtobrutinib), including the development of atrial fibrillation, hypertension, ventricular arrhythmias, sudden death, heart failure, bleeding, and ischemic complications (stroke and myocardial infarction). This review highlights hematological insights underlying cardiotoxicity, an area that has received limited attention in comparison to the predominantly cardiological perspective. This review synthesizes emerging evidence on hematological biomarkers, cardiotoxic mechanisms, and therapeutic interventions, linking hematology and cardiology to enhance understanding and guide comprehensive prevention and management strategies.</div></div>","PeriodicalId":56139,"journal":{"name":"Blood Reviews","volume":"70 ","pages":"Article 101268"},"PeriodicalIF":6.9,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069746","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 : 2025-01-22DOI: 10.1016/j.blre.2025.101269
Catherine H. Marshall , Emmanuel S. Antonarakis , Mrinal M. Patnaik
While radiotherapeutics have demonstrated significant clinical benefit across multiple cancer types including thyroid cancer, neuroendocrine tumors, and prostate cancer, hematological toxicities can be frequent and challenging. It remains unknown to what extent the hematologic toxicity is driven by clonal processes that preexist and are selected for by treatment induced selection pressures. In this review, we discuss the background leading to the adoption of radiotherapeutics in the treatment of solid tumor malignancies, the risk of hematologic toxicities and myeloid neoplasms and the evidence pointing to potential precursor lesions that may predispose patients to hematologic toxicities. Additionally, we discuss how prevalent clonal hematopoiesis is among patients with solid tumor malignancies and suggest workflows for patients with cytopenias or clonal hematopoiesis who are receiving or have received radiotherapeutic agents.
{"title":"Radiotherapeutics, clonal hematopoiesis, and risk of hematologic malignancies: The good, the bad, the ugly","authors":"Catherine H. Marshall , Emmanuel S. Antonarakis , Mrinal M. Patnaik","doi":"10.1016/j.blre.2025.101269","DOIUrl":"10.1016/j.blre.2025.101269","url":null,"abstract":"<div><div>While radiotherapeutics have demonstrated significant clinical benefit across multiple cancer types including thyroid cancer, neuroendocrine tumors, and prostate cancer, hematological toxicities can be frequent and challenging. It remains unknown to what extent the hematologic toxicity is driven by clonal processes that preexist and are selected for by treatment induced selection pressures. In this review, we discuss the background leading to the adoption of radiotherapeutics in the treatment of solid tumor malignancies, the risk of hematologic toxicities and myeloid neoplasms and the evidence pointing to potential precursor lesions that may predispose patients to hematologic toxicities. Additionally, we discuss how prevalent clonal hematopoiesis is among patients with solid tumor malignancies and suggest workflows for patients with cytopenias or clonal hematopoiesis who are receiving or have received radiotherapeutic agents.</div></div>","PeriodicalId":56139,"journal":{"name":"Blood Reviews","volume":"70 ","pages":"Article 101269"},"PeriodicalIF":6.9,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048802","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 : 2025-01-18DOI: 10.1016/j.blre.2025.101258
Danielle Guy , Robert Bagnall , Rebecca L. Morgan , Ifeoluwa Babatunde , Agathe Nevière , Gabriela Friedrich , Liga Bennetts , Omar Irfan , Isaac Odame
{"title":"Corrigendum to “Impact of transcranial Doppler screening on stroke prevention in children and adolescents with sickle cell disease: A systematic review and meta-analysis” [Blood Reviews (2024) 101253]","authors":"Danielle Guy , Robert Bagnall , Rebecca L. Morgan , Ifeoluwa Babatunde , Agathe Nevière , Gabriela Friedrich , Liga Bennetts , Omar Irfan , Isaac Odame","doi":"10.1016/j.blre.2025.101258","DOIUrl":"10.1016/j.blre.2025.101258","url":null,"abstract":"","PeriodicalId":56139,"journal":{"name":"Blood Reviews","volume":"70 ","pages":"Article 101258"},"PeriodicalIF":6.9,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017061","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 : 2025-01-11DOI: 10.1016/j.blre.2025.101257
Junyang Mei , Feng Jiao , Yiping Li , Jiujie Cui , Haiyan Yang , Liwei Wang
Cancer therapy-induced thrombocytopenia (CT-IT) is one of the most common hematological toxicities of anti-cancer therapy, often leading to treatment dose reduced, postponed, or treatment plans altered or even discontinued. Thrombopoietin (TPO) is the only key regulatory factor in platelet production, and TPO receptor is considered an ideal target for the treatment of thrombocytopenia. Thrombopoietic agents, including recombinant human thrombopoietin (rhTPO) and thrombopoietin receptor agonists (TPO-RAs), bind to different regions of the TPO receptor, activating downstream signaling pathways to increase platelet levels. In recent years, numerous studies have demonstrated the effectiveness of thrombopoietic agents in the management of CT-IT. These agents can reduce bleeding risk, decrease platelet transfusions, and maintain relative dose intensity (RDI) of anti-cancer treatments. This article provides a review of the current progress in the application of thrombopoietic agents for CT-IT management.
{"title":"Application of thrombopoietic agents in cancer therapy-induced thrombocytopenia: A comprehensive review","authors":"Junyang Mei , Feng Jiao , Yiping Li , Jiujie Cui , Haiyan Yang , Liwei Wang","doi":"10.1016/j.blre.2025.101257","DOIUrl":"10.1016/j.blre.2025.101257","url":null,"abstract":"<div><div>Cancer therapy-induced thrombocytopenia (CT-IT) is one of the most common hematological toxicities of anti-cancer therapy, often leading to treatment dose reduced, postponed, or treatment plans altered or even discontinued. Thrombopoietin (TPO) is the only key regulatory factor in platelet production, and TPO receptor is considered an ideal target for the treatment of thrombocytopenia. Thrombopoietic agents, including recombinant human thrombopoietin (rhTPO) and thrombopoietin receptor agonists (TPO-RAs), bind to different regions of the TPO receptor, activating downstream signaling pathways to increase platelet levels. In recent years, numerous studies have demonstrated the effectiveness of thrombopoietic agents in the management of CT-IT. These agents can reduce bleeding risk, decrease platelet transfusions, and maintain relative dose intensity (RDI) of anti-cancer treatments. This article provides a review of the current progress in the application of thrombopoietic agents for CT-IT management.</div></div>","PeriodicalId":56139,"journal":{"name":"Blood Reviews","volume":"70 ","pages":"Article 101257"},"PeriodicalIF":6.9,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985748","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 : 2025-01-11DOI: 10.1016/j.blre.2025.101256
Tingting Yue , Yue Sun , Yun Dai , Fengyan Jin
Multiple myeloma (MM) remains incurable and patients eventually face the relapse/refractory dilemma. B cell maturation antigen (BCMA)-targeted immunotherapeutic approaches have shown great effectiveness in patients with relapsed/refractory MM, mainly including chimeric antigen receptor T cells (CAR-T), bispecific T cell engagers (TCEs), and antibody-drug conjugates (ADCs). However, their impact on long-term survival remains to be determined. Nonetheless, resistance to these novel therapies is still inevitable, raising a challenge that we have never met in both laboratory research and clinical practice. In this scenario, the investigation aiming to enhance and prolong the anti-MM activity of BCMA-targeted therapies has been expanding rapidly. Despite considerable uncertainty in our understanding of the mechanisms for their resistance, they have mainly been attributed to antigen-dependency, T cell-driven factors, and (immune) tumor microenvironment. In this review, we summarize the current understanding of the mechanisms for resistance to BCMA-targeted immunotherapies and discuss potential strategies for overcoming it.
{"title":"Mechanisms for resistance to BCMA-targeted immunotherapies in multiple myeloma","authors":"Tingting Yue , Yue Sun , Yun Dai , Fengyan Jin","doi":"10.1016/j.blre.2025.101256","DOIUrl":"10.1016/j.blre.2025.101256","url":null,"abstract":"<div><div>Multiple myeloma (MM) remains incurable and patients eventually face the relapse/refractory dilemma. B cell maturation antigen (BCMA)-targeted immunotherapeutic approaches have shown great effectiveness in patients with relapsed/refractory MM, mainly including chimeric antigen receptor T cells (CAR-T), bispecific T cell engagers (TCEs), and antibody-drug conjugates (ADCs). However, their impact on long-term survival remains to be determined. Nonetheless, resistance to these novel therapies is still inevitable, raising a challenge that we have never met in both laboratory research and clinical practice. In this scenario, the investigation aiming to enhance and prolong the anti-MM activity of BCMA-targeted therapies has been expanding rapidly. Despite considerable uncertainty in our understanding of the mechanisms for their resistance, they have mainly been attributed to antigen-dependency, T cell-driven factors, and (immune) tumor microenvironment. In this review, we summarize the current understanding of the mechanisms for resistance to BCMA-targeted immunotherapies and discuss potential strategies for overcoming it.</div></div>","PeriodicalId":56139,"journal":{"name":"Blood Reviews","volume":"70 ","pages":"Article 101256"},"PeriodicalIF":6.9,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017064","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 : 2025-01-01DOI: 10.1016/j.blre.2024.101251
Geoffrey Shouse
Bispecific antibody therapy has revolutionized the treatment of hematologic malignancies. There are currently 7 FDA approved products with 4 different targets covering 5 indications in 4 diseases. Products include blinatumomab targeting B-cell ALL in MRD detectable first remission and in relapsed and/or refractory disease, elranatamab and teclistamab targeting BCMA in relapsed/refractory multiple myeloma, talquetamab targeting GPCR5D in multiple myeloma, and mosunetuzumab, epcoritamab and glofitamab which all target CD20 in follicular lymphoma, both follicular and large B cell lymphoma, or large B cell lymphoma alone, respectively. Each product utilizes the strategy of T-cell redirection by binding CD3 on the effector cell to target immune cells toward a tumor associated antigen. There are overlapping toxicities related to activation of the immune system and inflammation. The role of these agents in earlier lines of therapy and in novel combinations are under heavy investigation and their full utility and benefit in the treatment of hematologic malignancies is yet to be fully realized.
{"title":"Bispecific antibodies for the treatment of hematologic malignancies: The magic is T-cell redirection","authors":"Geoffrey Shouse","doi":"10.1016/j.blre.2024.101251","DOIUrl":"10.1016/j.blre.2024.101251","url":null,"abstract":"<div><div>Bispecific antibody therapy has revolutionized the treatment of hematologic malignancies. There are currently 7 FDA approved products with 4 different targets covering 5 indications in 4 diseases. Products include blinatumomab targeting B-cell ALL in MRD detectable first remission and in relapsed and/or refractory disease, elranatamab and teclistamab targeting BCMA in relapsed/refractory multiple myeloma, talquetamab targeting GPCR5D in multiple myeloma, and mosunetuzumab, epcoritamab and glofitamab which all target CD20 in follicular lymphoma, both follicular and large B cell lymphoma, or large B cell lymphoma alone, respectively. Each product utilizes the strategy of T-cell redirection by binding CD3 on the effector cell to target immune cells toward a tumor associated antigen. There are overlapping toxicities related to activation of the immune system and inflammation. The role of these agents in earlier lines of therapy and in novel combinations are under heavy investigation and their full utility and benefit in the treatment of hematologic malignancies is yet to be fully realized.</div></div>","PeriodicalId":56139,"journal":{"name":"Blood Reviews","volume":"69 ","pages":"Article 101251"},"PeriodicalIF":6.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775095","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}
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