Blood Cancer Journal最新文献_第6页

Bispecific antibodies in the treatment of multiple myeloma 治疗多发性骨髓瘤的双特异性抗体

IF 12.8 1区医学

Blood Cancer Journal Pub Date : 2024-09-12 DOI: 10.1038/s41408-024-01139-y

Anup Joseph Devasia, Ajai Chari, Guido Lancman

{"title":"Bispecific antibodies in the treatment of multiple myeloma","authors":"Anup Joseph Devasia, Ajai Chari, Guido Lancman","doi":"10.1038/s41408-024-01139-y","DOIUrl":"https://doi.org/10.1038/s41408-024-01139-y","url":null,"abstract":"The treatment paradigm in myeloma is constantly changing. Upfront use of monoclonal antibodies like daratumumab along with proteasome inhibitors (PI)s, and immune modulators (IMiD)s have significantly improved survival and outcomes, but also cause unique challenges at the time of relapse. Engaging immune T cells for tumour cell kill with chimeric antigenic T-cell (CAR T-cell) therapy and bispecific antibodies have become important therapeutic options in relapsed multiple myeloma. Bispecific antibodies are dual antigen targeting constructs that engage the T cells to plasma cells through various target antigens like B-cell membrane antigen (BCMA), G-protein-coupled receptor family C group 5 member D (GPRC5D), and Fc receptor-homolog 5 (FcRH5). These agents have proven to induce deep and durable responses in heavily pre-treated myeloma patients with a predictable safety profile and the ease of off-the-shelf availability. Significant research is ongoing to overcome resistance mechanisms like T cell exhaustion, target antigen mutation or loss and high disease burden. Various trials are also studying these agents as first line options in the newly diagnosed setting. These agents play an important role in the relapsed setting, and efforts are underway to optimize their sequencing in the myeloma treatment algorithm.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"18 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Belantamab mafodotin, pomalidomide, and dexamethasone for triple class exposed/refractory relapsed multiple myeloma: a subgroup analysis of the ALGONQUIN trial 贝仑单抗马福多汀、泊马度胺和地塞米松治疗三类暴露/难治性复发性多发性骨髓瘤：ALGONQUIN试验的亚组分析

IF 12.8 1区医学

Blood Cancer Journal Pub Date : 2024-09-11 DOI: 10.1038/s41408-024-01135-2

Arleigh McCurdy, Donna Reece, Martha L. Louzada, Darrell White, Stephen Parkin, Michael P. Chu, Rami Kotb, Hira Mian, Ibraheem Othman, Jiandong Su, Aniba Khan, Engin Gul, Suzanne Trudel

{"title":"Belantamab mafodotin, pomalidomide, and dexamethasone for triple class exposed/refractory relapsed multiple myeloma: a subgroup analysis of the ALGONQUIN trial","authors":"Arleigh McCurdy, Donna Reece, Martha L. Louzada, Darrell White, Stephen Parkin, Michael P. Chu, Rami Kotb, Hira Mian, Ibraheem Othman, Jiandong Su, Aniba Khan, Engin Gul, Suzanne Trudel","doi":"10.1038/s41408-024-01135-2","DOIUrl":"https://doi.org/10.1038/s41408-024-01135-2","url":null,"abstract":"Given the early use of triplet and quadruplet regimens, most patients with multiple myeloma (MM) will be exposed and/or refractory to PIs, IMiDs, and anti-CD38 mAbs after first- or second-line treatment. Effective treatment for this group of triple class exposed/refractory (TCE/R) patients is crucial. Here we present a post-hoc subgroup analysis of TCE/R patients treated on the ALGONQUIN study of belantamab mafodotin plus pomalidomide-dexamethasone (belamaf-Pd) for relapsed MM. Of the 99 patients treated on the ALGONQUIN study, 69 were TCE and 56 were TCR and were included in this analysis. Patients had a median of three prior lines of therapy. The ORR was 86.4% in TCE patients and 84.9% in TCR patients, with ≥ very good partial response rates of 64% and 68% respectively. The median progression free survival was 18.3 months in TCE patients and 19.6 months in TCR patients, with overall survival not yet reached and 34.4 months, respectively for TCE and TCR patients. No new safety signals were identified. The most common Grade ≥ 3 AEs were keratopathy (48%), decreased visual acuity (42%), neutropenia (36%), thrombocytopenia (27%), and infection (25%). In this subgroup analysis of the ALGONQUIN study, patients with TCE/TCR disease treated with belamaf-Pd achieved high clinical response rates with durable remissions, comparable to other novel therapeutics in this space.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"48 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Association of ADAM family members with proliferation signaling and disease progression in multiple myeloma ADAM 家族成员与多发性骨髓瘤的增殖信号转导和疾病进展的关系

IF 12.8 1区医学

Blood Cancer Journal Pub Date : 2024-09-11 DOI: 10.1038/s41408-024-01133-4

Marietheres Evers, Thorsten Stühmer, Martin Schreder, Torsten Steinbrunn, Martina Rudelius, Franziska Jundt, Regina Ebert, Tanja Nicole Hartmann, Ralf Christian Bargou, Andreas Rosenwald, Ellen Leich

{"title":"Association of ADAM family members with proliferation signaling and disease progression in multiple myeloma","authors":"Marietheres Evers, Thorsten Stühmer, Martin Schreder, Torsten Steinbrunn, Martina Rudelius, Franziska Jundt, Regina Ebert, Tanja Nicole Hartmann, Ralf Christian Bargou, Andreas Rosenwald, Ellen Leich","doi":"10.1038/s41408-024-01133-4","DOIUrl":"https://doi.org/10.1038/s41408-024-01133-4","url":null,"abstract":"Multiple myeloma (MM) is a hematological malignancy whose curability is greatly challenged by recurrent patient relapses and therapy resistance. We have previously proposed the high expression of ADAM8, ADAM9 and ADAM15 (A Disintegrin And Metalloproteinase 8/9/15) as adverse prognostic markers in MM. This study focused on the so far scarcely researched role of ADAM8/9/15 in MM using two patient cohorts and seven human MM cell lines (HMCL). High ADAM8/9/15 expression was associated with high-risk cytogenetic abnormalities and extramedullary disease. Furthermore, ADAM8/15 expression increased with MM progression and in relapsed/refractory MM compared to untreated patient samples. RNA sequencing and gene set enrichment analysis comparing ADAM8/9/15high/low patient samples revealed an upregulation of proliferation markers and proliferation-associated gene sets in ADAM8/9/15high patient samples. High ADAM8/9/15 expression correlated with high Ki67 and high ADAM8/15 expression with high MYC protein expression in immunohistochemical stainings of patient tissue. Conversely, siRNA-mediated knockdown of ADAM8/9/15 in HMCL downregulated proliferation-related gene sets. Western blotting revealed that ADAM8 knockdown regulated IGF1R/AKT signaling and ADAM9 knockdown decreased mTOR activation. Lastly, high ADAM8/9/15 expression levels were verified as prognostic markers independent of Ki67/MYC expression and/or high-risk abnormalities. Overall, these findings suggest that ADAM8/9/15 play a role in MM progression and proliferation signaling.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"31 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Global, regional, and national burden of Burkitt lymphoma from 1990 to 2021 and predictions to 2030: a systematic analysis for the Global Burden of Disease Study 2021 1990 年至 2021 年全球、地区和国家伯基特淋巴瘤负担及 2030 年预测：2021 年全球疾病负担研究的系统分析

IF 12.8 1区医学

Blood Cancer Journal Pub Date : 2024-09-09 DOI: 10.1038/s41408-024-01138-z

Ying Wang, Ziyuan Shen, Chenlu He, Xing Xing, Zaixiang Tan, Wei Sang

引用次数: 0

Phase II trial of elotuzumab with pomalidomide and dexamethasone for daratumumab-refractory multiple myeloma 艾洛妥珠单抗联合泊马度胺和地塞米松治疗达拉单抗难治性多发性骨髓瘤的II期试验

IF 12.8 1区医学

Blood Cancer Journal Pub Date : 2024-09-05 DOI: 10.1038/s41408-024-01134-3

Ricardo D. Parrondo, Betsy R. LaPlant, Jamie Elliott, Andre Fernandez, Caitlin J. Flott, Diedre Arrington, Dustin Chapin, Jade Brown, Saurav Das, Vivek Roy, Asher A. Chanan-Khan, Sikander Ailawadhi

引用次数: 0

Blood neurofilament light chain measurements in adults with CNS histiocytic neoplasms 中枢神经系统组织细胞瘤成人患者的血液神经丝蛋白轻链测量结果

IF 12.8 1区医学

Blood Cancer Journal Pub Date : 2024-09-05 DOI: 10.1038/s41408-024-01118-3

Samantha A. Banks, Paul Decker, Eoin P. Flanagan, Anastasia Zekeridou, Ronald S. Go, Jithma P. Abeykoon, Gaurav Goyal, Jason R. Young, Matthew J. Koster, Robert Vassallo, Jay H. Ryu, Caroline J. Davidge-Pitts, Aishwarya Ravindran, Julio C. Sartori Valinotti, N. Nora Bennani, Mithun V. Shah, Karen L. Rech, Corrie R. Bach, Jeanette E. Eckel-Passow, W. Oliver Tobin

引用次数: 0

Genome profiling with targeted adaptive sampling long-read sequencing for pediatric leukemia 利用靶向自适应采样长读数测序技术进行小儿白血病基因组图谱分析

IF 12.8 1区医学

Blood Cancer Journal Pub Date : 2024-08-28 DOI: 10.1038/s41408-024-01108-5

Shota Kato, Aiko Sato-Otsubo, Wataru Nakamura, Masahiro Sugawa, Ai Okada, Kenichi Chiba, Nao Takasugi, Tomoya Irikura, Moe Hidaka, Masahiro Sekiguchi, Kentaro Watanabe, Yuichi Shiraishi, Motohiro Kato

引用次数: 0

Increased risk of subsequent neoplasm after hematopoietic stem cell transplantation in 5-year survivors of childhood acute lymphoblastic leukemia 儿童急性淋巴细胞白血病 5 年存活者接受造血干细胞移植后罹患后续肿瘤的风险增加

IF 12.8 1区医学

Blood Cancer Journal Pub Date : 2024-08-28 DOI: 10.1038/s41408-024-01122-7

Aimée S. R. Westerveld, Pien Roesthuis, Helena J. H. van der Pal, Dorine Bresters, Marc Bierings, Jacqueline Loonen, Andrica C. H. de Vries, Marloes Louwerens, Maria M. W. Koopman, Marry M. van den Heuvel-Eibrink, Margriet van der Heiden-van der Loo, Peter Hoogerbrugge, Geert O. Janssens, Ronald R. de Krijger, Cecile M. Ronckers, Rob Pieters, Leontien C. M. Kremer, Jop C. Teepen

{"title":"Increased risk of subsequent neoplasm after hematopoietic stem cell transplantation in 5-year survivors of childhood acute lymphoblastic leukemia","authors":"Aimée S. R. Westerveld, Pien Roesthuis, Helena J. H. van der Pal, Dorine Bresters, Marc Bierings, Jacqueline Loonen, Andrica C. H. de Vries, Marloes Louwerens, Maria M. W. Koopman, Marry M. van den Heuvel-Eibrink, Margriet van der Heiden-van der Loo, Peter Hoogerbrugge, Geert O. Janssens, Ronald R. de Krijger, Cecile M. Ronckers, Rob Pieters, Leontien C. M. Kremer, Jop C. Teepen","doi":"10.1038/s41408-024-01122-7","DOIUrl":"https://doi.org/10.1038/s41408-024-01122-7","url":null,"abstract":"Acute lymphoblastic leukemia (ALL) survivors are at risk for developing subsequent neoplasms, but there is limited information on long-term risks and risk factors for both subsequent malignant neoplasms (SMNs) and subsequent non-malignant neoplasms (SNMNs). We analyzed long-term risk and risk factors for SMNs and SNMNs among 3291 5-year ALL survivors from the Dutch Childhood Cancer Survivor Study-LATER cohort (1963–2014). We calculated standardized incidence ratios (SIRs) and cumulative incidences and used multivariable Cox proportional hazard regression analyses for analyzing risk factors. A total of 97 survivors developed SMNs and 266 SNMNs. The 30-year cumulative incidence was 4.1% (95%CI: 3.5–5.3) for SMNs and 10.4%(95%CI: 8.9–12.1) for SNMNs. Risk of SMNs was elevated compared to the general population (SIR: 2.6, 95%CI: 2.1–3.1). Survivors treated with hematopoietic stem cell transplantation (HSCT) with total body irradiation (TBI) (HR:4.2, 95%CI: 2.3–7.9), and without TBI (HR:4.0,95%CI: 1.2–13.7) showed increased SMN risk versus non-transplanted survivors. Cranial radiotherapy (CRT) was also a risk factor for SMNs (HR:2.1, 95%CI: 1.4–4.0). In conclusion, childhood ALL survivors have an increased SMN risk, especially after HSCT and CRT. A key finding is that even HSCT-treated survivors without TBI treatment showed an increased SMN risk, possibly due to accompanied chemotherapy treatment. This emphasizes the need for careful follow-up of HSCT and/or CRT-treated survivors.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"34 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142085296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

B-cell intrinsic RANK signaling cooperates with TCL1 to induce lineage-dependent B-cell transformation B 细胞固有的 RANK 信号与 TCL1 相互配合，诱导线型依赖性 B 细胞转化

IF 12.8 1区医学

Blood Cancer Journal Pub Date : 2024-08-28 DOI: 10.1038/s41408-024-01123-6

Lisa Pfeuffer, Viola Siegert, Julia Frede, Leonie Rieger, Riccardo Trozzo, Niklas de Andrade Krätzig, Sandra Ring, Shamim Sarhadi, Nicole Beck, Stefan Niedermeier, Mar Abril-Gil, Mohamed Elbahloul, Marianne Remke, Katja Steiger, Ruth Eichner, Julia Jellusova, Roland Rad, Florian Bassermann, Christof Winter, Jürgen Ruland, Maike Buchner

{"title":"B-cell intrinsic RANK signaling cooperates with TCL1 to induce lineage-dependent B-cell transformation","authors":"Lisa Pfeuffer, Viola Siegert, Julia Frede, Leonie Rieger, Riccardo Trozzo, Niklas de Andrade Krätzig, Sandra Ring, Shamim Sarhadi, Nicole Beck, Stefan Niedermeier, Mar Abril-Gil, Mohamed Elbahloul, Marianne Remke, Katja Steiger, Ruth Eichner, Julia Jellusova, Roland Rad, Florian Bassermann, Christof Winter, Jürgen Ruland, Maike Buchner","doi":"10.1038/s41408-024-01123-6","DOIUrl":"https://doi.org/10.1038/s41408-024-01123-6","url":null,"abstract":"B-cell malignancies, such as chronic lymphocytic leukemia (CLL) and multiple myeloma (MM), remain incurable, with MM particularly prone to relapse. Our study introduces a novel mouse model with active RANK signaling and the TCL1 oncogene, displaying both CLL and MM phenotypes. In younger mice, TCL1 and RANK expression expands CLL-like B1-lymphocytes, while MM originates from B2-cells, becoming predominant in later stages and leading to severe disease progression and mortality. The induced MM mimics human disease, exhibiting features like clonal plasma cell expansion, paraproteinemia, anemia, and kidney and bone failure, as well as critical immunosurveillance strategies that promote a tumor-supportive microenvironment. This research elucidates the differential impacts of RANK activation in B1- and B2-cells and underscores the distinct roles of single versus combined oncogenes in B-cell malignancies. We also demonstrate that human MM cells express RANK and that inhibiting RANK signaling can reduce MM progression in a xenotransplantation model. Our study provides a rationale for further investigating the effects of RANK signaling in B-cell transformation and the shaping of a tumor-promoting microenvironment.<figure></figure>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"37 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142084730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Longitudinal assessment of established risk stratification models in patients with monoclonal gammopathy of undetermined significance. 对意义未定的单克隆丙种球蛋白病患者的既定风险分层模型进行纵向评估。

IF 12.9 1区医学

Blood Cancer Journal Pub Date : 2024-08-27 DOI: 10.1038/s41408-024-01126-3

Kosima Zuern, Thomas Hielscher, Annika Werly, Iris Breitkreutz, Sandra Sauer, Marc S Raab, Carsten Müller-Tidow, Hartmut Goldschmidt, Elias K Mai

{"title":"Longitudinal assessment of established risk stratification models in patients with monoclonal gammopathy of undetermined significance.","authors":"Kosima Zuern, Thomas Hielscher, Annika Werly, Iris Breitkreutz, Sandra Sauer, Marc S Raab, Carsten Müller-Tidow, Hartmut Goldschmidt, Elias K Mai","doi":"10.1038/s41408-024-01126-3","DOIUrl":"10.1038/s41408-024-01126-3","url":null,"abstract":"Risk of progression of monoclonal gammopathy of undetermined significance (MGUS) into multiple myeloma and related plasma cell disorders can be determined by three major risk stratification models, namely Mayo2005, Sweden2014, and NCI2019. This retrospective study of 427 patients with MGUS diagnosed according to the 2014 International Myeloma Working Group criteria aimed to describe and analyze the longitudinal applicability of these risk models. In all three models, the majority of patients remained at their baseline risk group, whereas small numbers of patients migrated to a different risk group. Proportions of patients among risk groups remained stable over time (e.g. Mayo2005 model, low-risk group, at baseline: 43%, after 1, 2, 3, 4, 5, and 8 years: 40%, 37%, 37%, 43%, 44%, and 43%). All three risk models reliably distinguished risk of progression at baseline, upon yearly reassessment (e.g. 1 year from diagnosis) and in time-dependent analyses. Upstaging to a high-risk category was associated with an increased risk of progression in all three models (Mayo2005: hazard ratio [HR] = 5.43, 95% confidence interval [95% CI] 1.21-24.39, p = 0.027; Sweden2014: HR = 13.02, 95% CI 5.25-32.28, p < 0.001; NCI2019: HR = 5.85, 95% CI 2.49-13.74, p < 0.001). Our study shows that MGUS risk stratification models can be applied longitudinally to repeatedly determine and improve individual risk of progression. Patient migration to higher risk categories during follow up should prompt more frequent monitoring in clinical routine.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"14 1","pages":"148"},"PeriodicalIF":12.9,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11349746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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