Blood Cancer Journal最新文献

{"title":"Docirbrutinib is a pan-mutant BTK inhibitor and inhibits B-cell receptor signaling in chronic lymphocytic leukemia cells in preclinical and early clinical investigations.","authors":"Natalia Timofeeva, Breana Herrera, Hitomi Fujiwara, Tokiko Asami, Hiroko Endo, Mariko Hatakeyama, Fumio Nakajima, Hiroshi Ohmoto, Yu Nishioka, Kyoko Miyamoto, Akinori Arimura, Shady I Tantawy, Javier Pinilla-Ibarz, Catherine C Coombs, Nitin Jain, Masaaki Sawa, Varsha Gandhi","doi":"10.1038/s41408-026-01509-8","DOIUrl":"https://doi.org/10.1038/s41408-026-01509-8","url":null,"abstract":"<p><p>BTK inhibitors (BTKi) have become standard of care for treatment of patients with chronic lymphocytic leukemia (CLL). Covalent BTKi (cBTKi) such as ibrutinib, acalabrutinib, and zanubrutinib are effective but alterations in the kinase domain at C481 or BTK gatekeeper residue T474 mutations result in development of resistance. Noncovalent BTK inhibitors (ncBTKi) such as pirtobrutinib are effective in patients with C481x mutations developed through use of cBTKi. However, resistance to ncBTKi can occur owing to second site aberrations in BTK, generating novel mutations such as L528x and T316x. Sometimes, CLL cells with double BTK mutations are also observed. These BTK aberrations underscore a need for new inhibitors that target pan-BTK-mutants. We evaluated the efficacy of a new ncBTKi, docirbrutinib (AS-1763), against 14 BTK mutants, including C481S, T474x, and L528x, as well as gatekeeper and kinase domain double mutants, using biochemical assays, cell-line models, and primary CLL lymphocytes. Docirbrutinib potently inhibited BTK autophosphorylation and mutant BTK-driven cell proliferation, with greater effects than ibrutinib and pirtobrutinib against certain mutants. In treatment-naïve and relapsed/refractory CLL samples, docirbrutinib disrupted B-cell receptor signaling and sensitized cells to apoptosis induced by venetoclax and AZD5991. In a dose-escalation trial (NCT05602363), docirbrutinib decreased CCL3/CCL4 biomarkers and inhibited the B-cell receptor pathway signaling in longitudinal samples from patients with relapsed/refractory CLL. These findings establish docirbrutinib as a pan-mutant ncBTKi with potential to improve outcomes for CLL patients, including those with disease resistant to cBTKi and other ncBTKi.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833067","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 phase II study of daratumumab and ibrutinib for relapsed/refractory chronic lymphocytic leukemia.","authors":"Ricardo D Parrondo, Sikander Ailawadhi, Betsy R Knopf, Ashley Zimmerman, Carly J Kasik, Dustin Chapin, Keisha Heslop, Vivek Roy, Aneel Paulus, Asher A Chanan-Khan","doi":"10.1038/s41408-026-01497-9","DOIUrl":"https://doi.org/10.1038/s41408-026-01497-9","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"16 1","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833074","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":"MGUS prevalence among active-duty military personnel.","authors":"Dickran Kazandjian, Christin DeStefano, Sarah Darmon, Alexander Dew, Elizabeth Hill, Katie Thoren, Ola Landgren","doi":"10.1038/s41408-026-01511-0","DOIUrl":"https://doi.org/10.1038/s41408-026-01511-0","url":null,"abstract":"<p><p>Monoclonal gammopathy of undetermined significance (MGUS) is a precursor condition for multiple myeloma, and although environmental exposures have been implicated in its pathogenesis, it is unknown whether exposure to open-air burn pits used during U.S. military operations in Iraq affects prevalence of MGUS in active-duty service members (ADSMs). ADSMs represent a distinct young and physically fit population, with higher proportions of male and Black individuals compared to the general U.S. population. This retrospective cohort study evaluated MGUS prevalence among ADSMs. Participants included ADSMs deployed to Iraq with self-reported burn pit exposure (DEP-IQ; n = 534), ADSMs deployed to Germany without burn pit exposure (DEP-DEU; n = 534), and non-deployed ADSMs (NON-DEP; n = 521). Eligibility criteria included deployment ≥180 days, age ≥35 years at deployment, and ≥10 years of continued military service. Serum samples collected 11-14 years post-deployment were analyzed using serum protein electrophoresis, immunofixation, and serum free light chain (sFLC) assays. MGUS and light-chain MGUS (LC-MGUS) prevalence were estimated using conventional and revised age-stratified sFLC reference intervals. MGUS + revised LC-MGUS prevalence did not differ between DEP-IQ (5.6%), DEP-DEU (4.3%), and NON-DEP (5.2%) cohorts. The overall total prevalence of MGUS + revised LC-MGUS was 5% and was higher in Black (10.4%) than White ADSMs (3.9%), p < 0.001. When using conventional sFLC reference intervals, LC-MGUS was more frequently identified among deployed ADSMs (1.6%) compared with non-deployed ADSMs (0.2%); however, this association was no longer significant when revised reference intervals were applied. These findings suggest that military service may involve cumulative or non-burn pit exposures contributing to plasma cell dysregulation. Application of updated sFLC reference ranges is critical to avoid overestimation of LC-MGUS. Long-term studies are warranted to define progression risk and inform targeted screening strategies in ADSMs.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833058","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":"Impact of thrombosis on disease progression, cancer and mortality in patients with essential thrombocythemia and polycythemia vera.","authors":"A Angona, B Cuevas, M Pérez-Encinas, F Ferrer-Marin, A Senín, E Arellano-Rodrigo, J C Hernández-Boluda, M I Mata Vázquez, G Caballero-Navarro, M T Gómez-Casares, E Magro, G Carreño-Tarragona, M A Cortés-Vázquez, R Pérez López, V García-Gutiérrez, M S Noya-Pereira, J M Alonso-Dominguez, C Sierra-Aisa, L Fox, C García Hernández, J M Guerra, E Cerezo, M Gasior, M Santaliestra, I Díez, M V Cuevas, L Sanz, I Pastor, R Stuckey, P Vélez, C Auría-Caballero, A Alvarez-Larrán","doi":"10.1038/s41408-026-01513-y","DOIUrl":"https://doi.org/10.1038/s41408-026-01513-y","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"16 1","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833113","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 effectiveness and safety of blinatumomab in adults with B-cell precursor acute lymphoblastic leukaemia across 13 European countries.","authors":"Sabina Chiaretti, Sabine Blum, Thibaut Leguay, Marie Balsat, Cyril Salek, Nicola Fracchiolla, Alexandros Spyridonidis, Anita Rijneveld, Cristina Papayannidis, Albertina Nunes, Anne Christine Wilke, Sigrid Machherndl-Spandl, Ulla Wartiovaara-Kautto, Jessica Choudhry, Ravikanth Maraboina, Gerhard Zugmaier, Noemi Mergen, Andreas Ochs, Alessandro Rambaldi","doi":"10.1038/s41408-026-01506-x","DOIUrl":"10.1038/s41408-026-01506-x","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"16 1","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810937","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":"A differentiated effector T cell repertoire defines a functionally high-risk group of smoldering myeloma patients.","authors":"Ross S Firestone, Anish K Simhal, Theresia Akhlaghi, Jung Hun Oh, Devin McAvoy, Kylee H Maclachlan, Juan-Jose Garces, Sham Mailankody, Hani Hassoun, Urvi A Shah, Neha Korde, Carlyn R Tan, Sridevi Rajeeve, Hamza Hashmi, Alexander M Lesokhin, Kinga Hosszu, Francesco Maura, Joseph O Deasy, Saad Z Usmani, Malin Hultcrantz","doi":"10.1038/s41408-026-01486-y","DOIUrl":"https://doi.org/10.1038/s41408-026-01486-y","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"16 1","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810874","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":"Peripheral blood cfDNA detection using clonoSEQ assay in multiple myeloma is concordant with bone marrow and clinical biomarkers.","authors":"J E Wiedmeier-Nutor, H E Kosiorek, M Arribas, H Simmons, A Jacob, S S Bhattu, R Fonseca, L Bruins, G Ahmann, U Yadav, S Chhabra, P L Bergsagel, R Fonseca","doi":"10.1038/s41408-026-01508-9","DOIUrl":"https://doi.org/10.1038/s41408-026-01508-9","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"16 1","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13133390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810831","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":"Efficacy and safety of talquetamab in relapsed/refractory multiple myeloma and renal impairment: a quaternary cancer center cohort.","authors":"Hossam M Ali, Sandra Mazzoni, Utkarsh Goel, Jack Khouri, Faiz Anwer, Louis S Williams, Diana Basali, Christy J Samaras, Beth M Faiman, Willem Van Heeckeren, Kimberly Hamilton, Joslyn Rudoni, Mikhaila Rice, Jonathan Kissam, Cynthia Scott, Saveta Mathur, Alexandra McDonald, Tara Roy, Julie Bevacqua, Marcelo C Pasquini, Jason Valent, Shahzad Raza","doi":"10.1038/s41408-026-01512-z","DOIUrl":"10.1038/s41408-026-01512-z","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"16 1","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13128851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761400","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":"Immune effector cell-associated enterocolitis post-BCMA directed CAR T-cell therapy: insights from a multicenter case series.","authors":"Sandra Susanibar-Adaniya,Benjamin A Derman,Adam D Cohen,Dan T Vogl,Shambavi Richard,Adriana Rossi,Matthew J Frigualt,Andrew J Yee,Binod Dhakal,Noffar Bar","doi":"10.1038/s41408-026-01473-3","DOIUrl":"https://doi.org/10.1038/s41408-026-01473-3","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"1 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147754641","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":"Mantle cell lymphoma outcomes following sequential first-line bendamustine-rituximab and second-line Bruton's tyrosine kinase inhibitor therapy.","authors":"Yucai Wang,Melissa C Larson,Steven R Hwang,Diego Villa,Laveniya Kugathasan,Anita Kumar,Ashlee Joseph,Taylor R Brooks,Brian T Hill,David A Bond,Kami J Maddocks,Alexey Danilov,Christine Argao,Jia Ruan,Imran A Nizamuddin,Brad S Kahl,Natalie S Grover,Nazneen B Khan,Georgios N Pongas,Izidore S Lossos,Evguenia Ouchveridze,Aung M Tun,Firas Baidoun,Muhamad Alhaj Moustafa,Zoey I Harris,Javier L Munoz,Philip R Young,Craig A Portell,Patrick M Reagan,Christine E Ryan,Reid W Merryman,Arash Velayati,I Brian Greenwell,Drew G Gerber,Preetesh Jain,Michael L Wang,Sabarish R Ayyappan,Eric Mou,Lauren G Banaszak,Priyanka A Pophali,Anthony C Stack,Marcus R Messmer,Mayur S Narkhede,Amitkumar Mehta,Tamara K Moyo,Nilanjan Ghosh,Rahul S Bhansali,Stefan K Barta,Manali K Kamdar,Jacob Anna,Alexander V Stanisic,Reem Karmali,Matthew J Maurer,James R Cerhan,Jonathon B Cohen,Peter Martin","doi":"10.1038/s41408-026-01507-w","DOIUrl":"https://doi.org/10.1038/s41408-026-01507-w","url":null,"abstract":"Addition of Bruton's tyrosine kinase inhibitor (BTKi) to first-line (1 L) bendamustine-rituximab (BR) improved progression-free survival (PFS) in patients with mantle cell lymphoma (MCL) in the SHINE and ECHO trials. We investigated whether sequential treatment with 1 L BR and second-line (2 L) BTKi can result in similar cumulative PFS compared to BR-BTKi combination therapy, using a multicenter cohort of 755 patients treated with 1 L BR between 2014 and 2020. Event-free survival (EFS), EFS2, and overall survival (OS) were analyzed. By intention-to-treat (ITT), EFS2 was defined as time from 1 L BR start to progression/relapse or retreatment following 2 L BTKi or death. After a median follow-up of 61.4 (95% CI 56.4-65.9) months, the median EFS after 1 L BR was 34.2 (95% CI 31.5-38.4) months. The median EFS2 following 1 L BR and 2 L BTKi by ITT analysis was 64.8 (95% CI 56.7-82.8) months, and the 5-year OS rate after 1 L BR was 57.9% (95% CI 54.1-62.0%), close to SHINE and ECHO results. Patients without high-risk features (high simplified MIPI, high Ki-67, blastoid/pleomorphic morphology, TP53 mutation, or complex karyotype) had more favorable survival outcomes. These results suggest that sequential treatment with 1 L BR and 2 L BTKi remains reasonable for select patients with MCL, particularly those without high-risk features.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"2 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147743895","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}