Blood Cancer Journal最新文献

{"title":"Clonal plasma cell proportion in the synthetic phase identifies a unique high-risk cohort in multiple myeloma","authors":"Saurabh Zanwar, Dragan Jevremovic, Prashant Kapoor, Horatiu Olteanu, Francis Buadi, Pedro Horna, Wilson Gonsalves, Gregory Otteson, Abiola Bukunmi Bolarinwa, Suzanne Hayman, Nadine Abdallah, Moritz Binder, Joselle Cook, Angela Dispenzieri, David Dingli, Morie A. Gertz, Taxiarchis Kourelis, Nelson Leung, Yi Lin, Eli Muchtar, Rahma Warsame, Amie Fonder, Miriam Hobbs, Yi Lisa Hwa, Michelle Rogers, Robert A. Kyle, S. Vincent Rajkumar, Shaji Kumar","doi":"10.1038/s41408-025-01232-w","DOIUrl":"https://doi.org/10.1038/s41408-025-01232-w","url":null,"abstract":"<p>Risk stratification models based on cytogenetics and disease burden help identify high-risk patients with newly diagnosed multiple myeloma (NDMM). However, some high-risk patients remain undetected. This study evaluated the prognostic utility of the proportion of clonal plasma cells in the S-phase of the cell cycle for NDMM. Patients with active multiple myeloma diagnosed between 01/01/2013 and 01/31/2023 who underwent S-phase assessment were included. The S-phase proportion was calculated by analyzing DNA content between G0/G1 and G2/M peaks. Among 823 patients, 16% (135) had S-phase ≥2% at diagnosis. Patients with S-phase ≥2% exhibited significantly worse median progression-free survival (PFS) of 1.4 years (95% CI: 1.2–1.9) compared to 2.9 years (95% CI: 2.6–3.3) for those with S-phase &lt;2% (HR 1.6, <i>p</i> &lt; 0.0001). Median overall survival (OS) was also significantly lower at 3.9 years (95% CI: 2.9–5.7) versus 9.2 years (95% CI: 7.9–not reached; HR 2.2, <i>p</i> &lt; 0.0001). Multivariate analysis confirmed S-phase ≥2% as an independent predictor of inferior PFS (HR 1.56, <i>p</i> = 0.001) and OS (HR 2, <i>p</i> &lt; 0.0001) after adjusting for R2-ISS risk, age, renal function, and treatment strategies. Among patients with S-phase ≥2%, 53% (68/129) experienced progression-free survival (PFS) under 18 months with upfront therapy. Elevated S-phase was associated with a 2.5-fold higher risk of progression within 18 months [OR 2.55 (95% CI: 1.7–3.7), <i>p</i> &lt; 0.001]. Patients with elevated S-phase but no IMS-high risk had a median OS of 5.7 years (95% CI: 4.7–9.2), similar to the IMS-high risk cohort without elevated S-phase (5.4 years, 95% CI: 4–NR). Those with both elevated S-phase and IMS-high risk had significantly worse OS (3.1 years, 95% CI: 1.6–NR, <i>p</i> = 0.043). These findings suggest that S-phase ≥2% is a powerful, independent prognostic marker for NDMM.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"10 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434915","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}

{"title":"Correction: A simplified, two-factor clinical prognostic scoring system for patients with newly diagnosed Hodgkins Lymphoma.","authors":"Charanpreet Singh, Lekshmon Ks, Arihant Jain, Deepesh Lad, Alka Khadwal, Rajender Basher, Amanjit Bal, Radhika Srinivasan, Subhash Varma, Pankaj Malhotra, Gaurav Prakash","doi":"10.1038/s41408-025-01221-z","DOIUrl":"10.1038/s41408-025-01221-z","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"15 1","pages":"18"},"PeriodicalIF":12.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412906","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}

{"title":"Decitabine with etoposide is effective in TP53 mutated myeloid tumors via overcoming differentiation block.","authors":"Jiexian Ma, Shunrong Sun, Yanhui Xie, Songlin Zhou, Min Wu, Xinyu Zuo, Mixue Xie, Xiaoqin Wang","doi":"10.1038/s41408-025-01228-6","DOIUrl":"10.1038/s41408-025-01228-6","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"15 1","pages":"19"},"PeriodicalIF":12.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412845","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}

{"title":"Comparing the efficacy and safety of venetoclax combined with hypomethylating agents versus intensive chemotherapy as induction therapy in newly diagnosed core binding factor acute myeloid leukemia patients","authors":"Jingyi Shen, Meng Shan, Mengqian Chu, Yiming Cai, Jingwen Rui, Suning Chen, Depei Wu, Yang Xu","doi":"10.1038/s41408-025-01227-7","DOIUrl":"https://doi.org/10.1038/s41408-025-01227-7","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"52 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143385123","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}

{"title":"Defining 'Intention' in intention-to-treat survival outcomes for chimeric antigen receptor T-cell therapy.","authors":"Charles J Milrod, Rebecca Steuer, Ari Pelcovits","doi":"10.1038/s41408-025-01220-0","DOIUrl":"10.1038/s41408-025-01220-0","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"15 1","pages":"16"},"PeriodicalIF":12.9,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11807103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373708","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}

{"title":"The clinical journey of belantamab mafodotin in relapsed or refractory multiple myeloma: lessons in drug development","authors":"Pralay Mukhopadhyay, Hesham A. Abdullah, Joanna B. Opalinska, Prani Paka, Eric Richards, Katja Weisel, Suzanne Trudel, Maria-Victoria Mateos, Meletios Athanasios Dimopoulos, Sagar Lonial","doi":"10.1038/s41408-025-01212-0","DOIUrl":"https://doi.org/10.1038/s41408-025-01212-0","url":null,"abstract":"<p>Patients with relapsed/refractory multiple myeloma (RRMM) have a poor prognosis and a need remains for novel effective therapies. Belantamab mafodotin, an anti–B-cell maturation antigen antibody-drug conjugate, was granted accelerated/conditional approval for patients with RRMM who have received at least 4 prior lines of therapy, based on response rates observed in DREAMM-1/DREAMM-2. Despite the 41% response rate and durable responses observed with belantamab mafodotin in the Phase III confirmatory DREAMM-3 trial, the marketing license for belantamab mafodotin was later withdrawn from US and European markets when the trial did not meet its primary endpoint of superiority for progression-free survival compared with pomalidomide and dexamethasone. This review reflects on key lessons arising from the clinical journey of belantamab mafodotin in RRMM. It considers how incorporating longer follow-up in DREAMM-3 may have better captured the clinical benefits of belantamab mafodotin, particularly given its multimodal, immune-related mechanism of action with responses deepening over time. A non-inferiority hypothesis may have been more appropriate rather than superiority in the context of a monotherapy versus an active doublet therapy. Further, anticipation of, and planning for, non-proportional hazards arising from response heterogeneity may have mitigated loss of statistical power. With the aim of improving the efficacy of belantamab mafodotin, other Phase III trials in the RRMM development program (DREAMM-7 and DREAMM-8) proceeded to evaluate the synergistic potential of combination regimens in earlier lines of treatment. The aim was to increase the proportion of patients responding to belantamab mafodotin (and thus the likelihood of seeing a clear separation of the progression-free survival curve versus comparator regimens). Protocol amendments reflecting DREAMM-3 learnings could also be implemented prospectively on the combinations trials to optimize the follow-up duration and mitigate risk. The wider implications of the lessons learned for clinical research in RRMM and in earlier treatment settings are discussed.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"32 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143258585","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}

{"title":"Genomic characterization of chronic lymphocytic leukemia in patients of African ancestry","authors":"Cecilia Bonolo de Campos, Chantal E. McCabe, Laura A. Bruins, Daniel R. O’Brien, Sochilt Brown, Renee C. Tschumper, Cristine Allmer, Yuan Xiao Zhu, Kari G. Rabe, Sameer A. Parikh, Neil E. Kay, Huihuang Yan, James R. Cerhan, John N. Allan, Richard R. Furman, J. Brice Weinberg, Danielle M. Brander, Diane F. Jelinek, Marta Chesi, Susan L. Slager, Esteban Braggio","doi":"10.1038/s41408-024-01207-3","DOIUrl":"https://doi.org/10.1038/s41408-024-01207-3","url":null,"abstract":"<p>Despite the considerable effort to characterize the genomic landscape of chronic lymphocytic leukemia (CLL), published data have been almost exclusively derived from patients of European Ancestry (EA), with significant underrepresentation of minorities, including patients of African Ancestry (AA). To begin to address this gap, we evaluated whether differences exist in the genetic and transcriptomic features of 157 AA and 440 EA individuals diagnosed with CLL. We sequenced 59 putative driver genes and found an increased frequency of high-impact mutations in AA CLL, including genes of the DNA damage repair (DDR) pathway. Telomere erosion was also increased in AA CLL, amplifying the notion of increased genomic instability in AA CLL. Furthermore, we found transcription enrichment of the Tumor Necrosis Factor-alpha (TNFα) Signaling via NF-κB pathway in AA CLL compared to EA CLL, suggesting that tumor promoting inflammation plays an important role in AA CLL. In summary, these results suggest that genomic instability and NF-kB activation is more prevalent in AA CLL than EA CLL.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"61 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192022","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}

{"title":"Implications of isolated MRD progression in newly diagnosed multiple myeloma treated with quadruplet therapy","authors":"Luciano J. Costa, Eva Medvedova, Binod Dhakal, Bhagirathbhai R. Dholaria, Kelly N. Godby, Susan Bal, Gayathri Ravi, Smith Giri, Saurabh Chhabra, Rebecca Silbermann, Natalie S. Callander","doi":"10.1038/s41408-025-01219-7","DOIUrl":"https://doi.org/10.1038/s41408-025-01219-7","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"11 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192023","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}

{"title":"Exploring BCL2 regulation and upstream signaling transduction in venetoclax resistance in multiple myeloma: potential avenues for therapeutic intervention","authors":"Rodrigo Fonseca, Yuan Xiao Zhu, Laura A. Bruins, Joseph Ahmann, Cecilia de Bonolo Campos, Esteban Braggio, Xianfeng Chen, Mariano Arribas, Susie Darvish, Seth Welsh, Erin Meermeier, Kiran K. Mangalaparthi, Richard K. Kandasamy, Greg Ahmann, J. Erin Wiedmeier-Nutor, Akhilesh Pandey, Marta Chesi, P. Leif Bergsagel, Rafael Fonseca","doi":"10.1038/s41408-025-01215-x","DOIUrl":"https://doi.org/10.1038/s41408-025-01215-x","url":null,"abstract":"<p>Investigating venetoclax (VTX) resistance in multiple myeloma (MM) is crucial for the development of novel therapeutic strategies to tackle resistance. We conducted a multi-omic characterization of established VTX-resistant isogenic human myeloma cell lines (HMCL) and primary MM patient samples pre- and post-VTX treatment. Transcriptomic and proteomic analysis revealed that resistance was largely associated with BCL-2 family protein dysregulation, including upregulation of anti-apoptotic proteins such as MCL-1, BCL-XL, BCL-2, and downregulation of pro-apoptotic members. Notably, the re-introduction of BIM into resistant cells restored VTX sensitivity and synergized with MCL-1 inhibitors. Upstream signaling pathways, including growth factor receptor tyrosine kinase (RTK) and phosphoinositide-3-kinase (PI3K) were implicated in this dysregulation. Simultaneous inhibition of MCL-1, BCL-XL, and upstream PI3K, RTK (FGF, EGF, and IGF1) mediated signaling enhanced VTX sensitivity. Post-translational modifications of MCL-1, particularly its stabilization via acetylation and phosphorylation, were investigated, although their inhibition only marginally increased VTX sensitivity. Lastly, the inhibition of AURKA and mitochondrial respiration also improved VTX sensitivity in some resistant HMCLs. Our findings suggest that combining VTX with MCL-1 and BCL-XL inhibitors or PIK3/RTK inhibitors holds potential for overcoming resistance. The study illustrates the importance of understanding molecular determinants of resistance to develop tailored therapeutic strategies.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"11 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143125399","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}

{"title":"Efficacy and safety of CAR-T cell therapy in B-ALL patients previously treated with blinatumomab","authors":"Yurou Chu, Biqi Zhou, Rui Gao, Miao Miao, Huiying Qiu, Xiaowen Tang, Ying Wang, Suning Chen, Liqing Kang, Depei Wu, Yang Xu","doi":"10.1038/s41408-025-01217-9","DOIUrl":"https://doi.org/10.1038/s41408-025-01217-9","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"111 7 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143125404","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}