Blood Cancer Journal最新文献

Fedratinib for the treatment of myelofibrosis: a critical appraisal of clinical trial and “real-world” data 治疗骨髓纤维化的费瑞替尼：对临床试验和 "真实世界 "数据的批判性评估

IF 12.8 1区医学

Blood Cancer Journal Pub Date : 2025-01-14 DOI: 10.1038/s41408-025-01211-1

Adrian Duek, Ilona Leviatan, Osnat Jarchowsky Dolberg, Martin H. Ellis

{"title":"Fedratinib for the treatment of myelofibrosis: a critical appraisal of clinical trial and “real-world” data","authors":"Adrian Duek, Ilona Leviatan, Osnat Jarchowsky Dolberg, Martin H. Ellis","doi":"10.1038/s41408-025-01211-1","DOIUrl":"https://doi.org/10.1038/s41408-025-01211-1","url":null,"abstract":"Fedratinib is a predominantly JAK2 inhibitor that has shown efficacy in untreated and ruxolitinib-exposed patients with myelofibrosis (MF). Based on randomized clinical trial data, it is approved for use in patients with International Prognostic Scoring System (IPSS) or Dynamic International Prognostic Scoring System (DIPSS) intermediate-2 or high-risk disease and is distinguished from ruxolitinib in that it can be administered without dose reduction in patients with thrombocytopenia, to a platelet count above 50,000/µL. In these trials, fedratinib achieved significant spleen volume reduction in ~30–45% of patients and improvement in total symptom scores in 35–40% with good tolerability. In contrast, recently published real-world data suggest that these responses may not be as robust outside clinical trials. In the context of routine clinical practice spleen responses are documented in only 13–68%, with varying degrees of symptom improvement. This may be due to the lack of a uniform definition of ruxolitinib failure, which may influence the timing of initiating fedratinib as a second-line treatment and result in a more prolonged exposure to ruxolitinib prior to intitaing fedratinib treatment. We suggest that given the growing number of drugs available for use in MF, recognizing the failure of first-line (and potentially subsequent) treatments is critical to allow timely transition to potentially more active agents, as highlighted by the data pertaining to fedratinib.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"1 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974708","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

Whole genome sequencing and the genetics of extramedullary disease in multiple myeloma

IF 12.8 1区医学

Blood Cancer Journal Pub Date : 2025-01-12 DOI: 10.1038/s41408-024-01208-2

Nicholas Bingham, Jaynish Shah, Daniel Wong, Sueh-li Lim, Krystal Bergin, Anna Kalff, Antonia Reale, Tiffany Khong, Sridurga Mithraprabhu, Andrew Spencer

引用次数: 0

Diverse real-life outcomes after intensive risk-adapted therapy for 1034 AML patients from the CETLAM Group

IF 12.8 1区医学

Blood Cancer Journal Pub Date : 2025-01-11 DOI: 10.1038/s41408-024-01205-5

Guadalupe Oñate, Ana Garrido, Montserrat Arnan, Helena Pomares, Ester Alonso, Mar Tormo, Marina Diaz-Beya, Susana Vives, Lurdes Zamora, Antonia Sampol, Rosa Coll, Olga Salamero, Marta Cervera, Antoni Garcia, Ferran Vall-Llovera, Sara Garcia-Avila, Joan Bargay, Xavier Ortin, Eva Iranzo, Francisca Guijarro, Marta Pratcorona, Josep F. Nomdedeu, Jordi Esteve, Jorge Sierra

{"title":"Diverse real-life outcomes after intensive risk-adapted therapy for 1034 AML patients from the CETLAM Group","authors":"Guadalupe Oñate, Ana Garrido, Montserrat Arnan, Helena Pomares, Ester Alonso, Mar Tormo, Marina Diaz-Beya, Susana Vives, Lurdes Zamora, Antonia Sampol, Rosa Coll, Olga Salamero, Marta Cervera, Antoni Garcia, Ferran Vall-Llovera, Sara Garcia-Avila, Joan Bargay, Xavier Ortin, Eva Iranzo, Francisca Guijarro, Marta Pratcorona, Josep F. Nomdedeu, Jordi Esteve, Jorge Sierra","doi":"10.1038/s41408-024-01205-5","DOIUrl":"https://doi.org/10.1038/s41408-024-01205-5","url":null,"abstract":"Given the heterogeneity of acute myeloid leukemia patients, it is necessary to identify patients considered fit for intensive therapy but who will perform poorly, and in whom alternative approaches deserve investigation. We analyzed 1034 fit adults ≤70 years intensively treated between 2012 and 2022 in the CETLAM group. Young adults ( ≤ 60 years) presented higher remission rates and improved survival than older adults above that age (CR 79% vs. 73%; p = 0.03 and 4-yr OS 53% vs. 33%; p < 0.001). Remission and survival outcomes varied among different genetic subsets. An especially adverse genetic group included complex, monosomal karyotype, TP53 alterations (deleted/mutated), and MECOMr. Transplant feasibility in this very adverse risk group was low, and OS and EFS at 4 years were 14% and 12%, in contrast to 70% and 57% in the favorable group and 38% and 32% in all other patients. We integrated clinical and genetic data into the Intensive Chemotherapy Score for AML (ICSA) with 6-risk categories with significantly different remission rates and OS, validated in another cohort of 581 AML patients from a previous CETLAM protocol. In summary, we identified groups of fit patients that benefit differently from an intensive approach which may be helpful in future treatment decisions.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"29 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961661","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

Tunneling nanotubes between bone marrow stromal cells support transmitophagy and resistance to apoptosis in myeloma

IF 12.8 1区医学

Blood Cancer Journal Pub Date : 2025-01-09 DOI: 10.1038/s41408-025-01210-2

Antonio Giovanni Solimando, Francesco Di Palma, Vanessa Desantis, Angelo Vacca, Maria Svelto, Francesco Pisani

引用次数: 0

Treatment with obinutuzumab plus venetoclax reshapes the TRB repertoire of CLL patients

IF 12.8 1区医学

Blood Cancer Journal Pub Date : 2025-01-07 DOI: 10.1038/s41408-025-01209-9

Paul J. Hengeveld, Joyce Schilperoord-Vermeulen, P. Martijn Kolijn, Julie M. N. Dubois, Peter E. Westerweel, Sabina Kersting, Arnon P. Kater, Mark-David Levin, Anton W. Langerak

引用次数: 0

Updated analysis of EMN02 demonstrated overall survival benefit to early ASCT for multiple myeloma.

IF 12.9 1区医学

Blood Cancer Journal Pub Date : 2025-01-03 DOI: 10.1038/s41408-024-01198-1

Alfred L Garfall

引用次数: 0

Integration of clinical outcomes and molecular features in extramedullary disease in multiple myeloma

IF 12.8 1区医学

Blood Cancer Journal Pub Date : 2024-12-23 DOI: 10.1038/s41408-024-01190-9

Rie Nakamoto-Matsubara, Valentina Nardi, Nora Horick, Tsuyoshi Fukushima, Ryan S. Han, Rajib Shome, Kiyosumi Ochi, Cristina Panaroni, Keertik Fulzele, Farah Rexha, Andrew R. Branagan, Diana Cirstea, Andrew J. Yee, David T. Scadden, Noopur S. Raje

{"title":"Integration of clinical outcomes and molecular features in extramedullary disease in multiple myeloma","authors":"Rie Nakamoto-Matsubara, Valentina Nardi, Nora Horick, Tsuyoshi Fukushima, Ryan S. Han, Rajib Shome, Kiyosumi Ochi, Cristina Panaroni, Keertik Fulzele, Farah Rexha, Andrew R. Branagan, Diana Cirstea, Andrew J. Yee, David T. Scadden, Noopur S. Raje","doi":"10.1038/s41408-024-01190-9","DOIUrl":"https://doi.org/10.1038/s41408-024-01190-9","url":null,"abstract":"Multiple myeloma (MM) remains incurable despite novel therapeutics. A major contributor to the development of relapsed/refractory and resistant MM is extraosseous extramedullary disease (EMD), whose molecular biology is still not fully understood. We analyzed 528 MM patients who presented to our institution between 2014 and 2021 and who had undergone molecular testing. We defined EMD as organ plasmacytoma distinct from bones and evaluated patients for the development of EMD with the goal of defining their molecular characteristics. Here, we show that RAS/BRAF mutations are likely essential for the development of EMD. Our results also indicate that the underlying reason for the negative outcomes in patients with poor prognostic factors such as duplication 1q and deletion 17p is largely due to the development of EMD. However, the presence of TP53 mutation remains a poor prognostic factor regardless of EMD development. Furthermore, mutation sites of TP53 were different between EMD versus non-EMD patients, with gain-of-function mutations enriched in patients with EMD. Our data highlights distinct molecular abnormalities in patients with EMD and provides potential mechanistic insights for novel therapeutic targets for the future.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"280 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873942","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 disparities in drug-related adverse events of patients with multiple myeloma: a pharmacovigilance study

IF 12.8 1区医学

Blood Cancer Journal Pub Date : 2024-12-20 DOI: 10.1038/s41408-024-01206-4

Majid Jaberi-Douraki, Xuan Xu, Danai Dima, Sikander Ailawadhi, Faiz Anwer, Sandra Mazzoni, Jason Valent, Muhammad Hamza Habib, Jim E. Riviere, Shahzad Raza

{"title":"Global disparities in drug-related adverse events of patients with multiple myeloma: a pharmacovigilance study","authors":"Majid Jaberi-Douraki, Xuan Xu, Danai Dima, Sikander Ailawadhi, Faiz Anwer, Sandra Mazzoni, Jason Valent, Muhammad Hamza Habib, Jim E. Riviere, Shahzad Raza","doi":"10.1038/s41408-024-01206-4","DOIUrl":"https://doi.org/10.1038/s41408-024-01206-4","url":null,"abstract":"Multiple myeloma (MM) is a complex hematological malignancy of clonal plasma cells driven by alterations to the chromosomal material leading to uncontrolled proliferation in the bone marrow. Ethnic and racial disparities persist in the prevalence, diagnosis, management, and outcomes of MM. These disparities are multifaceted and intersect with various factors, including demographics, geography, socioeconomic status, genetics, and access to healthcare. This study utilized the openFDA human drug adverse events (AEs) to analyze global data pertaining to MM patients and patterns of treatment-related AEs. We identified ten most frequently used drugs and drug regimens in six distinct regions, including North America (NA), Europe (EU), Asia (AS), Africa (AF), Oceania (OC), and Latin America & the Caribbean (LA). AE patterns were evaluated using the reporting odds ratio combined with a 95% confidence interval. AE reports were more prevalent in men than in women across all regions. Cardiotoxicities were more likely observed in AS and EU, while secondary neoplasms were more frequently reported in the EU. Nephropathies were prominent in OC, AF (in males), and AS (in females), while vascular toxicity, including embolism and thrombosis, was more common in NA (in males). A notable improvement in survival, particularly in AS, EU, and NA, with a significant decline in death rates was observed. Hospitalization rates displayed less variation in AS and EU but exhibited more pronounced fluctuations in AF, LA, and OC. In conclusion, this comprehensive analysis offers valuable insights into the demographic, geographic, and AE patterns of MM patients across the globe.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"69 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142858430","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

Clinical characteristics and outcomes of 476 mantle cell lymphoma patients aged 80 years and older

IF 12.8 1区医学

Blood Cancer Journal Pub Date : 2024-12-19 DOI: 10.1038/s41408-024-01204-6

Simon Pahnke, Kossi D. Abalo, Sara Ekberg, Alexandra Albertsson-Lindblad, Karin E. Smedby, Mats Jerkeman, Ingrid Glimelius

引用次数: 0

Expanded tumor-associated polymorphonuclear myeloid-derived suppressor cells in Waldenstrom macroglobulinemia display immune suppressive activity Waldenstrom 巨球蛋白血症患者体内扩增的肿瘤相关多形核髓源性抑制细胞具有免疫抑制活性

IF 12.8 1区医学

Blood Cancer Journal Pub Date : 2024-12-18 DOI: 10.1038/s41408-024-01173-w

Vaishali Bhardwaj, Zhi-Zhang Yang, Shahrzad Jalali, Jose C. Villasboas, Rekha Mudappathi, Junwen Wang, Prithviraj Mukherjee, Jonas Paludo, Xinyi Tang, Hyo Jin Kim, Jordan E. Krull, Kerstin Wenzl, Anne J. Novak, Patrizia Mondello, Stephen M. Ansell

{"title":"Expanded tumor-associated polymorphonuclear myeloid-derived suppressor cells in Waldenstrom macroglobulinemia display immune suppressive activity","authors":"Vaishali Bhardwaj, Zhi-Zhang Yang, Shahrzad Jalali, Jose C. Villasboas, Rekha Mudappathi, Junwen Wang, Prithviraj Mukherjee, Jonas Paludo, Xinyi Tang, Hyo Jin Kim, Jordan E. Krull, Kerstin Wenzl, Anne J. Novak, Patrizia Mondello, Stephen M. Ansell","doi":"10.1038/s41408-024-01173-w","DOIUrl":"https://doi.org/10.1038/s41408-024-01173-w","url":null,"abstract":"The role of the bone marrow (BM) microenvironment in regulating the antitumor immune response in Waldenstrom macroglobulinemia (WM) remains poorly understood. Here we transcriptionally and phenotypically profiled non-malignant (CD19- CD138-) BM cells from WM patients with a focus on myeloid derived suppressive cells (MDSCs) to provide a deeper understanding of their role in WM. We found that HLA-DRlowCD11b+CD33+ MDSCs were significantly increased in WM patients as compared to normal controls, with an expansion of predominantly polymorphonuclear (PMN)-MDSCs. Single-cell immunogenomic profiling of WM MDSCs identified an immune-suppressive gene signature with upregulated inflammatory pathways associated with interferon and tumor necrosis factor (TNF) signaling. Gene signatures associated with an inflammatory and immune suppressive environment were predominately expressed in PMN-MDSCs. In vitro, WM PMN-MDSCs demonstrated robust T-cell suppression and their viability and expansion was notably enhanced by granulocyte colony stimulating factor (G-CSF) and TNFα. Furthermore, BM malignant B-cells attracted PMN-MDSCs to a greater degree than monocytic MDSCs. Collectively, these data suggest that malignant WM B cells actively recruit PMN-MDSCs which promote an immunosuppressive BM microenvironment through a direct T cell inhibition, while release of G-CSF/TNFα in the microenvironment further promotes PMN-MDSC expansion and in turn immune suppression. Targeting PMN-MDSCs may therefore represent a potential therapeutic strategy in patients with WM.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"42 2 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841071","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