Blood Cancer Journal最新文献

{"title":"Outcomes of patients with relapsed/refractory lymphoplasmacytic lymphoma/waldenström macroglobulinemia treated with venetoclax: a multicenter retrospective analysis","authors":"Y. Sawalha, S. Sarosiek, R. L. Welkie, S. Seif, S. Thapa, S. Zanwar, K. Cahill, R. Treitman, H. Shah, S. Arora, G. Pongas, A. Winter, A. Major, P. A. Riedell, M. L. Palomba, P. Kapoor, A. Grajales-Cruz, K. H. Shain, S. K. Thomas, J. J. Castillo","doi":"10.1038/s41408-025-01271-3","DOIUrl":"https://doi.org/10.1038/s41408-025-01271-3","url":null,"abstract":"<p>Venetoclax showed promising activity in a small phase II trial in relapsed/refractory Waldenström macroglobulinemia (WM). To report the clinical activity of venetoclax and prognostic factors associated with outcomes in a larger cohort, we retrospectively identified 76 patients with relapsed/refractory lymphoplasmacytic lymphoma (LPL)/WM treated with venetoclax monotherapy at nine US medical centers. The median age at venetoclax treatment initiation was 66 years. <i>MYD88, CXCR4</i>, and <i>TP53</i> mutations were detected in 65 (94%), 23 (40%), and 10 (22%) patients, respectively. The median number of prior lines of treatment was 3, including covalent BTK inhibitor in 82% and alkylating agent in 71% of patients. The overall and major response rates to venetoclax were 70% and 63%, respectively. The median and 2-year progression-free survival (PFS) were 28.5 months and 57%, respectively. The median and 2-year overall survival were not reached and 82%, respectively. Prior treatment with BTK inhibitor was the only factor associated with PFS in multivariate analysis (hazard ratio 2.97, p = 0.012). Venetoclax dose interruptions and/or reductions occurred in 27 patients (41%). Five patients (7%) developed laboratory tumor lysis syndrome (TLS), including 3 (4%) with clinical TLS. Venetoclax resulted in a high response rate and a prolonged PFS in patients with heavily pretreated LPL/WM.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"13 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831795","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":"Cardiovascular adverse events and outcomes after anti-BCMA CAR-T for relapsed and refractory multiple myeloma","authors":"Stefanie Palfi, Lauren C. Peres, Himara Koelmeyer, Melissa Alsina, Rachid C. Baz, Brandon J. Blue, Salvatore Corallo, Gabriel De Avila, Ciara Freeman, Rebecca Gonzalez, Ariel Grajales-Cruz, Kristy Harvey, Hien D. Liu, Taiga Nishihori, Guilherme H. Oliveira, Laura B. Oswald, Omar Castaneda Puglianini, Sruthi Selvakumar, Alexis Behne Sharma, Elicia Wang, Kenneth H. Shain, Michael Jain, Frederick L. Locke, Mohammed Alomar, Doris K. Hansen, Dae Hyun Lee","doi":"10.1038/s41408-025-01261-5","DOIUrl":"https://doi.org/10.1038/s41408-025-01261-5","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"81 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827637","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":"CAR T-cell therapy response varies by extranodal disease site in large B-cell lymphoma","authors":"Alejandro Luna, Sean M. Devlin, Kai Rejeski, Jessica R. Flynn, Magdalena Corona, Efrat Luttwak, Alfredo Rivas-Delgado, Ivan Landego, Giulio Cassanello, Marina Gomez-Llobell, Sandeep S. Raj, Parastoo B. Dahi, Richard J. Lin, Allison Parascondola, M.Lia Palomba, Gunjan L. Shah, Michael Scordo, Ana Alarcon Tomas, Doris Leithner, Akshay Bedmutha, Heiko Schöder, Brandon S. Imber, Gilles Salles, Jae H. Park, Miguel-Angel Perales, Roni Shouval","doi":"10.1038/s41408-025-01273-1","DOIUrl":"https://doi.org/10.1038/s41408-025-01273-1","url":null,"abstract":"<p>The role of extranodal (EN) sites as potential sanctuary regions resistant to CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy in large B-cell lymphoma (LBCL) remains unclear. To investigate this, we retrospectively analyzed 283 adults treated with commercial CD19 CAR-T therapy, assessing 958 PET-CT scans across four time points: pre-apheresis, pre-lymphodepletion, best response, and relapse. EN involvement prior to CAR-T therapy was common (76%). Outcomes for patients with exclusive EN disease were similar to those with nodal (ND) disease alone; however, patients with concomitant EN and ND disease (EN + ND) had lower complete response rates and shorter progression-free survival. Site-specific outcomes varied: lungs/pleura/pericardium and gastrointestinal/peritoneum involvement had the lowest local response rates (48% and 51%, respectively). Notably, the risk of same-site relapse was highest in the lungs/pleura/pericardium (hazard ratio [HR] 7.8) and gastrointestinal/peritoneum (HR 5.97). Among patients relapsing after CAR-T, two-year overall survival rates from time of relapse were significantly lower in those with EN relapse (23% for exclusive EN; 25% for EN + ND) compared to exclusive ND relapse (64%; <i>p</i> = 0.008). These findings underscore the high prevalence of EN disease in CAR-T recipients and its site-specific impact on outcomes, highlighting the need for organ-targeted strategies to enhance treatment efficacy.</p><figure><p>Differential site-specific response and relapse/progression risk according to pre-CAR-T therapy anatomical site involvement in Large B-cell Lymphoma. Risk of site-specific relapse or progression was not evaluable for CNS/orbital/cranial sinuses, adrenal/genitourinary, hepatobiliary/pancreas, and spleen due to insufficient number of events.</p></figure>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"5 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831796","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":"Mendelian randomization of immune cell phenotypes to discover potential drug targets for B-cell malignancy","authors":"Sina A. Beer, Molly Went, Charlie Mills, Codie Wood, Amit Sud, James M. Allan, Richard Houlston, Martin F. Kaiser","doi":"10.1038/s41408-025-01277-x","DOIUrl":"https://doi.org/10.1038/s41408-025-01277-x","url":null,"abstract":"<p>Although treatment options for B-cell malignancies have expanded, many patients continue to face limited response rates, highlighting an urgent need for new therapeutic targets. To prioritize candidate drug targets for B-cell malignancies, we employed Mendelian Randomization to estimate potentially causal relationships between 445 immune cell traits and six B-cell cancers: follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), Hodgkin lymphoma (HL), marginal zone lymphoma (MZL), chronic lymphocytic leukemia (CLL), and multiple myeloma (MM), totaling 22,922 cases and 394,204 controls. 163 traits showed a suggestive association with at least one B-cell malignancy (<i>P</i> &lt; 0.05), with 34 traits being significant after correction for multiple testing (<i>P</i> &lt; 2 × 10⁻⁴). By integrating findings with observational data and clinical trial evidence to support drug target candidacy, 24 cell surface markers were identified as druggable targets. In addition to established therapeutic targets such as CD3, CD20 and CD38, our analysis highlights BAFF-R and CD39 in HL, CD25 in MM, CD27 in CLL, CD80/86 in DLBCL, and CCR2 in FL and MZL as promising candidates for therapeutic inhibition. Our findings provide further support for the potential of human genetics to guide the identification of drug targets and address a productivity-limiting step.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"59 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805666","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":"Real-world treatment patterns for teclistamab and talquetamab in multiple myeloma (MM): experience from 609 patients","authors":"Farheen Chunara, Chris Lugo, Kristen Osinski, Mansi R. Shah, Nishi Shah, Jessica Kent, Ghulam Rehman Mohyuddin, Sabarinath Venniyil Radhakrishnan, Gurbakhash Kaur, Rajshekhar Chakraborty, Rahul Banerjee, Leo Rasche, Carolina Schinke, Anita D’Souza, Aniko Szabo, Meera Mohan","doi":"10.1038/s41408-025-01254-4","DOIUrl":"https://doi.org/10.1038/s41408-025-01254-4","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"31 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805670","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":"Real-world experience with first-line CPX-351 treatment in patients with acute myeloid leukemia – long-term follow-up with focus on younger patients","authors":"Christina Rautenberg, Jan Moritz Middeke, Christoph Röllig, Matthias Stelljes, Verena Gaidzik, Oliver Kriege, Mareike Verbeek, Katrin Koch, Julia Marie Unglaub, Felicitas Thol, Stefan W. Krause, Mathias Hänel, Charlotte Neuerburg, Vladan Vucinic, Christian-Friedrich Jehn, Maxi Wass, Michael Heuser, Lars Fransecky, Jens Chemnitz, Udo Holtick, Kerstin Schäfer-Eckart, Josephine Schröder, Sabrina Kraus, William Krüger, Ulrich Kaiser, Sebastian Scholl, Guido Kobbe, Paul Sebastian Jäger, Nael Alakel, Malte von Bonin, Katja Sockel, Maher Hanoun, Uwe Platzbecker, Tobias A. W. Holderried, Anke Morgner, Tim Sauer, Katharina S. Götze, Eva Wagner-Drouet, Konstanze Döhner, Hartmut Döhner, Christoph Schliemann, Johannes Schetelig, Martin Bornhäuser, Ulrich Germing, Sara Flossdorf, Thomas Schroeder, Friedrich Stölzel","doi":"10.1038/s41408-025-01274-0","DOIUrl":"https://doi.org/10.1038/s41408-025-01274-0","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"183 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797646","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":"A Real-World International Staging System (RW-ISS) for patients with newly diagnosed multiple myeloma","authors":"Christian Brieghel, Tobias Schmidt Slørdahl, Morten Nørgaard Andersen, Agoston Gyula Szabo, Carsten Utoft Niemann, Sigrún Thorsteinsdóttir","doi":"10.1038/s41408-025-01268-y","DOIUrl":"https://doi.org/10.1038/s41408-025-01268-y","url":null,"abstract":"<p>The revised international staging system (R-ISS) in multiple myeloma (MM) was recently updated as the second R-ISS (R2-ISS) and refined prognostication in clinical trial populations. By including 2929 Danish patients with MM and complete data on R2-ISS registered from 2005 through 2019, we validated the R2-ISS for overall survival (OS) in a population-based cohort; however, only partly among younger patients. We thus developed a real-world international staging system (RW-ISS) from a 75% training cohort. Feature selection and weighted scores of high-risk variables from a Cox regression model of OS included age &gt;70 years (2 points), performance status (PS) &gt; 1 (2 points), PS 1 (1 point), t(14;16) (1 point), ISS III (1 point), ISS II (0.5 points), high lactate dehydrogenase (0.5 points), and del(17p) (0.5 points). In the test set, patients with RW-ISS I (0–2.0 points, 38.2%), II (2.5–3.0 points, 19.8%), III (3.5–4.5 points, 27.1%), and IV (5.0–7.0 points, 15.0%) demonstrated a median OS of 9.5, 5.5, 3.4, and 1.1 years, respectively (<i>P</i> &lt; 0.0001) and the C-index was superior for RW-ISS as compared to both R2-ISS and R-ISS (0.708 vs 0.604 vs 0.595, respectively). RW-ISS was in part externally validated. We thus recommend using RW-ISS in routine clinical care of NDMM.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"89 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797880","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":"Molecular characteristics and clinical implications of TP53 mutations in therapy-related myelodysplastic syndromes","authors":"Zefei Bao, Bing Li, Tiejun Qin, Zefeng Xu, Shiqiang Qu, Yujiao Jia, Chengwen Li, Lijuan Pan, Qingyan Gao, Meng Jiao, Huijun Wang, Qi Sun, Zhijian Xiao","doi":"10.1038/s41408-025-01276-y","DOIUrl":"https://doi.org/10.1038/s41408-025-01276-y","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"25 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143790102","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":"Venetoclax-based treatment combinations in relapsed/refractory multiple myeloma: practice patterns and impact of secondary cytogenetic abnormalities on outcomes","authors":"Abiola Bolarinwa, Madhu Nagaraj, Saurabh Zanwar, Nadine Abdallah, P. Leif Bergsagel, Moritz Binder, Francis Buadi, Saurabh Chhabra, Joselle Cook, David Dingli, Angela Dispenzieri, Morie A. Gertz, Wilson Gonsalves, Suzanne Hayman, Prashant Kapoor, Taxiarchis Kourelis, Nelson Leung, Yi Lin, Eli Muchtar, Ricardo Parrondo, Vivek Roy, Taimur Sher, Mustaqeem Siddiqui, Rahma Warsame, Amie Fonder, Miriam Hobbs, Yi Lisa Hwa, Michelle Rogers, Udit Yadav, J. Erin Wiedmeier-Nutor, Linda B. Baughn, S. Vincent Rajkumar, Rafael Fonseca, Sikander Ailawadhi, Shaji Kumar","doi":"10.1038/s41408-025-01264-2","DOIUrl":"https://doi.org/10.1038/s41408-025-01264-2","url":null,"abstract":"<p>Venetoclax (Ven), a BCL-2 inhibitor, has demonstrated efficacy in patients with relapsed/refractory multiple myeloma (RRMM) harboring a t(11;14) and/or elevated BCL-2 expression. However, data from clinical trial remain inconclusive. This retrospective study evaluated the efficacy and safety of Ven-based therapies in 232 MM patients without concurrent AL amyloidosis treated at Mayo Clinic sites between Jan 2015 and Dec 2023. The median age was 62 years, with a median of 3 prior lines of therapy. Among the cohort, 82% had t(11;14), and elevated BCL-2 expression was identified in 17 of 18 non-t(11;14) patients tested. Ven combinations included Ven-Dex (VenD; 48.3%), Proteasome Inhibitor-Ven (30.2%), and Daratumumab-Ven (19%) with other combinations making up the rest. The overall response rate was 57%; 64% for t(11;14) patients and 26% for non-t(11;14) patients. Median progression-free survival (PFS) was 9.4 months overall; 11.8 months for t(11;14) patients and 2.9 months for those without (<i>p</i> &lt; 0.001). Among t(11;14) patients, the presence of del(17p) or 1q gain/amplification significantly reduced PFS to 7.7 months. Venetoclax-based regimens remain an important option for t(11;14) patients, but efficacy is limited in patients without a t(11;14). The presence of secondary high-risk cytogenetics imparts an inferior PFS.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"141 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775555","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":"Real-world evaluation of teclistamab for the treatment of relapsed/refractory multiple myeloma (RRMM): an International Myeloma Working Group Study","authors":"Carlyn Rose Tan, Sireesha Asoori, Chiung-Yu Huang, Larissa Brunaldi, Rakesh Popat, Efstathios Kastritis, Joaquin Martinez-Lopez, Radhika Bansal, Andre De Menezes Silva Corraes, Saurabh Chhabra, Ricardo Parrondo, Sikander Ailawadhi, Despina Fotiou, Meletios A. Dimopoulos, Kwee Yong, Catriona Mactier, Chris Lau, Magdalena Corona, Adolfo Jesús Sáez Marin, Hira Mian, Brian GM. Durie, Saad Z. Usmani, Thomas G. Martin, Yi Lin","doi":"10.1038/s41408-025-01259-z","DOIUrl":"https://doi.org/10.1038/s41408-025-01259-z","url":null,"abstract":"<p>Teclistamab, a BCMAxCD3-directed bispecific antibody, has shown high response rates and durable remissions in triple-class-exposed patients with relapsed/refractory multiple myeloma. We performed a retrospective study evaluating the efficacy and safety of teclistamab in 210 patients treated at 9 academic centers from five countries within the IMWG Immunotherapy Working Group Committee. Patients were heavily pretreated, with 83% having triple-class refractory disease and 44% with prior BCMA-targeted therapy. With a median follow-up of 5.3 months, the overall response rate (ORR) was 67% in 188 response-evaluable patients, including 55% with a very good partial response or better. The 6-month progression-free survival (PFS) and overall survival rates were 53% (95% CI, 46–61%) and 73% (67–80%), respectively. Patients who received prior BCMA-directed therapy compared to BCMA-treatment-naïve patients had a lower ORR (58.3 vs 74.0%; <i>P</i> = 0.03) and PFS (6-month PFS 43% [95% CI, 33–55%] vs 63% [54–73%]; logrank <i>P</i> = 0.004). Step-up dosing occurred in an outpatient setting for 23% of patients. CRS occurred in 54% of patients, and infections were reported in 56.2% of patients, with 22% having grade ≥3 infections. In this multicenter real-world study, we found that teclistamab can lead to rapid responses in heavily pretreated myeloma patients with comparable efficacy and safety profiles, as demonstrated in MajesTEC-1.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"774 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766568","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}