Blood最新文献

{"title":"Genomic Determinants of Response and Resistance to Pirtobrutinib in Relapsed/Refractory Chronic Lymphocytic Leukemia.","authors":"Jennifer R Brown,Bastien Nguyen,Sai Prasad Desikan,Helen Won,Shady I Tantawy,Samuel C McNeely,Narasimha Marella,Hetal S Randeria,Lauren M Hanson,Andrew Parker,Salome Calado Botelho,Jennifer A Woyach,Krish Patel,Constantine S Tam,Toby A Eyre,Chan Y Cheah,Nirav N Shah,Paolo Ghia,Wojciech Jurczak,Minna Balbas,Binoj Chandrasekharan Nair,Paolo B Abada,Chunxiao Wang,Denise Wang,Lindsey Elizabeth Roeker,Varsha Gandhi,William G Wierda","doi":"10.1182/blood.2024027009","DOIUrl":"https://doi.org/10.1182/blood.2024027009","url":null,"abstract":"Pirtobrutinib, a non-covalent, reversible Bruton tyrosine kinase inhibitor (BTKi), demonstrated efficacy in patients with chronic lymphocytic leukemia (CLL), resistant to covalent BTKi (cBTKi). Genomic correlations with response and resistance to pirtobrutinib were analyzed in relapsed/refractory (R/R) CLL patients pretreated with cBTKi and enrolled in the phase 1/2 BRUIN trial. DNA sequencing was performed on PBMCs at baseline, on treatment, and at progressive disease (PD). Common alterations at baseline included mutations in BTK (43%), TP53 (38%), SF3B1 (25%), NOTCH1 (23%), ATM (19%), XPO1 (11%), PLCG2 (9%), BCL2 (8%) and 17p deletion (28%). Common baseline BTK mutations included C481S (85%), C481R (10%), C481F (6%) and C481Y (4%). At PD, 60/88 patients (68%) acquired ≥1 mutation, including 44% with acquired BTK mutations and 24% with other acquired mutations. A total of 55 acquired BTK mutations were detected in 39 patients, including gatekeeper mutations (T474I/F/S/L/Y/P, 26%), kinase-impaired L528W (16%), C481F/R/Y (5%), V416L (2%), and A428D (1%) and others proximal to the ATP-binding pocket, D539G/H/A (1%) and Y545N (1%). Decrease or complete clearance of BTK C481x was observed at PD in 36/43 patients (84%). Using a more sensitive assay, 37% (18/49) of acquired BTK mutations were detected at baseline at low allele frequency. Using the highly sensitive assay at progression, a similar frequency of acquired BTK mutations (39%) was detected, and all patients had detectable acquired mutations. This study highlights the complex clonal dynamics of BTK mutations in R/R CLL patients undergoing pirtobrutinib treatment, and the extent of resistance without an obvious genomic driver. NCT03740529.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"109 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235750","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":"Rebalancing the hemophilia teeter-totter.","authors":"Thomas C Abshire","doi":"10.1182/blood.2025030260","DOIUrl":"https://doi.org/10.1182/blood.2025030260","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"146 14","pages":"1631-1632"},"PeriodicalIF":23.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205602","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":"More than skin deep.","authors":"Ryan A Wilcox","doi":"10.1182/blood.2025030356","DOIUrl":"https://doi.org/10.1182/blood.2025030356","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"146 14","pages":"1635-1636"},"PeriodicalIF":23.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205531","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-DLI for ALL, but not without lymphodepletion.","authors":"Lutz P Müller","doi":"10.1182/blood.2025030291","DOIUrl":"https://doi.org/10.1182/blood.2025030291","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"32 1","pages":"1632-1634"},"PeriodicalIF":20.3,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203946","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":"Remission conversion drives outcomes after CAR T-cell therapy for multiple myeloma: a registry analysis from the DRST.","authors":"Maximilian Merz, Nico Gagelmann, Samih Smaili, Sarah Flossdorf, Sandra Sauer, Christof Scheid, Bastian von Tresckow, Gerald Wulf, Katja Weisel, Igor Wolfgang Blau, Monika Engelhardt, Ralph Wäsch, Natalie Schub, Raphael Teipel, Judith Hecker, Johannes Waldschmidt, Britta Besemer, Ben-Niklas Baermann, Simon Call, Leo Hansmann, Francis Ayuketang Ayuk, Marc S Raab, Hermann Einsele, Uwe Platzbecker, Nicolaus Kröger","doi":"10.1182/blood.2025028330","DOIUrl":"10.1182/blood.2025028330","url":null,"abstract":"<p><strong>Abstract: </strong>Cellular therapies targeting B-cell maturation antigen have shown promise in controlled clinical trials, but their impact in broader, diverse patient populations remains underexplored. This study examines the real-world efficacy and safety in 343 triple-class-exposed patients with relapsed and refractory multiple myeloma who received idecabtagene vicleucel (ide-cel; n = 266) or ciltacabtagene autoleucel (cilta-cel; n = 77) after >3 previous lines of therapy in Germany. Cilta-cel, compared with ide-cel, demonstrated superior outcomes, achieving a higher overall response rate (94% vs 82%) and 10-month progression-free survival (PFS; 76% vs 47%). Cilta-cel also led to higher complete response (CR; 61% vs 39%) and improved response conversion, with more patients achieving CR after starting from less than CR before chimeric antigen receptor T-cell (CAR T) therapy. For those attaining CR after therapy, cilta-cel showed longer PFS, especially in patients who entered treatment with a partial response or worse. Cytokine release syndrome was observed in 85% of cilta-cel and 81% of ide-cel cases, predominantly low grade. Immune effector cell-associated neurotoxicity syndrome was more common with cilta-cel (25% vs 15%), although nonrelapse mortality at 10 months was comparable between therapies (7% vs 5%). Weighted multivariable analysis after propensity score matching confirmed a significant advantage in terms of PFS for cilta-cel, with a hazard ratio of 0.48. Overall, outcomes in our registry analysis were comparable with the pivotal trials that led to approval of the respective agents. Cilta-cel demonstrated a greater capacity for response conversion and durable remission. These findings underscore the need for individualized CAR T therapy selection to optimize patient outcomes.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"1677-1686"},"PeriodicalIF":23.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282369","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":"Foxo1 unlocks the liver endothelial code to iron sensing.","authors":"Kostas Pantopoulos","doi":"10.1182/blood.2025030281","DOIUrl":"https://doi.org/10.1182/blood.2025030281","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"14 1","pages":"1639-1641"},"PeriodicalIF":20.3,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203947","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":"DRiving STandard-of-care CAR T cells in real-world Germany.","authors":"Mark R Dowling,Simon J Harrison","doi":"10.1182/blood.2025029932","DOIUrl":"https://doi.org/10.1182/blood.2025029932","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"157 1","pages":"1634-1635"},"PeriodicalIF":20.3,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203948","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":"AML halts neutrophil maturation.","authors":"Lakshmi Sandhow, Diana Passaro","doi":"10.1182/blood.2025030403","DOIUrl":"https://doi.org/10.1182/blood.2025030403","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"146 14","pages":"1638-1639"},"PeriodicalIF":23.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205539","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":"In low-risk myelodysplastic syndrome, don't shoot the STAG2.","authors":"Natasha Szuber,Lambert Busque","doi":"10.1182/blood.2025030114","DOIUrl":"https://doi.org/10.1182/blood.2025030114","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"2 1","pages":"1636-1638"},"PeriodicalIF":20.3,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203949","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":"Marstacimab prophylaxis in hemophilia A/B without inhibitors: results from the phase 3 BASIS trial.","authors":"Davide Matino, Andrew Palladino, Carrie Turich Taylor, Eunhee Hwang, Sangeeta Raje, Satyaprakash Nayak, Regina McDonald, Suchitra S Acharya, Johnny Mahlangu, Victor Jiménez-Yuste, Nirmalkumar Choraria, Renchi Yang, Chi-Kong Li, Murtadha Al-Khabori, Yasser Wali, Javier Morales Adrián, Young-Shil Park, O Bülent Zülfikar, John Teeter","doi":"10.1182/blood.2024027468","DOIUrl":"10.1182/blood.2024027468","url":null,"abstract":"<p><strong>Abstract: </strong>Marstacimab targets the tissue factor pathway inhibitor to rebalance hemostasis. Previous phase 1 and 2 trials established marstacimab safety and efficacy in adults with severe hemophilia A (HA) or B (HB). BASIS is an open-label, marstacimab phase 3 trial in males aged 12 to 74 years with severe HA (factor VIII <1%) or moderately severe to severe HB (factor IX ≤2%). Participants without inhibitors received on-demand (OD) or routine prophylaxis (RP) therapy during a 6-month observational phase (OP) before receiving once-weekly subcutaneous 150 mg marstacimab during a 12-month active treatment phase (ATP). Primary end points were annualized bleeding rate (ABR) for treated bleeds vs previous OD or RP during the OP, and safety. Of 128 participants enrolled in the OP, 116 received marstacimab in the ATP. In the OD group (n = 33), mean ABR decreased from 39.86 (95% confidence interval [CI], 33.05-48.07) in the OP to 3.20 (95% CI, 2.10-4.88) in the ATP, demonstrating superiority of marstacimab (estimated ABR ratio, 0.080 [95% CI, 0.057-0.113]; P < .0001). In the RP group (n = 83), mean ABR decreased from 7.90 (95% CI, 5.14-10.66) in the OP to 5.09 (95% CI, 3.40-6.78) in the ATP, demonstrating noninferiority and superiority of marstacimab (estimated ABR difference, -2.81 [95% CI, -5.42 to -0.20]; P = .0349). There were no deaths or thromboembolic events. Weekly subcutaneous marstacimab reduced ABR vs OD or RP therapy in the OP in individuals with severe HA or moderately severe to severe HB without inhibitors. Marstacimab was safe and well tolerated with no unanticipated side effects. This trial was registered at www.clinicaltrials.gov as #NCT03938792.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"1654-1663"},"PeriodicalIF":23.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559141","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}