Lixin Wang, Chuling Fang, Qingzheng Kang, Wenfa Huang, Ziren Chen, Weiqiang Zhao, Lei Wang, Yiran Wang, Kun Tan, Xiao Guo, Yuanyuan Xu, Shuhong Wang, Lijun Wang, Jingqiao Qiao, Zhixiong Tang, Chuan Yu, Yang Xu, Yisheng Li, Li Yu
{"title":"Bispecific CAR-T cells targeting CD19/20 in patients with relapsed or refractory B cell non-Hodgkin lymphoma: a phase I/II trial.","authors":"Lixin Wang, Chuling Fang, Qingzheng Kang, Wenfa Huang, Ziren Chen, Weiqiang Zhao, Lei Wang, Yiran Wang, Kun Tan, Xiao Guo, Yuanyuan Xu, Shuhong Wang, Lijun Wang, Jingqiao Qiao, Zhixiong Tang, Chuan Yu, Yang Xu, Yisheng Li, Li Yu","doi":"10.1038/s41408-024-01105-8","DOIUrl":"10.1038/s41408-024-01105-8","url":null,"abstract":"<p><p>Non-Hodgkin lymphoma (NHL) is a common malignancy in the hematologic system, and traditional therapy has limited efficacy for people with recurrent/refractory NHL (R/R NHL), especially for patients with diffuse large B cell lymphoma (DLBCL). Chimeric antigen receptor (CAR) T-cell therapy is a novel and effective immunotherapy strategy for R/R hematopoietic malignancies, but relapses can occur due to the loss of CAR-T cells in vivo or the loss of antigen. One strategy to avoid antigen loss after CAR-T cell therapy is to target one more antigen simultaneously. Tandem CAR targeting CD19 and CD22 has demonstrated the reliability of tandem CAR-T cell therapy for R/R B-ALL. This study explores the therapeutic potential of tandem CD19/20 CAR-T in the treatment of R/R B cell NHL. The efficacy and safety of autologous CD19/20 CAR-T cells in eleven R/R B cell NHL adult patients were evaluated in an open-label, single-arm trial. Most patients achieved complete response, exhibiting the efficacy and safety of tandem CD19/20 CAR-T cells. The TCR repertoire diversity of CAR-T cells decreased after infusion. The expanded TCR clones in vivo were mainly derived from TCR clones that had increased expression of genes associated with immune-related signaling pathways from the infusion product (IP). The kinetics of CAR-T cells in vivo were linked to an increase in the expression of genes related to immune response and cytolysis/cytotoxicity.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"14 1","pages":"130"},"PeriodicalIF":12.9,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11306243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900829","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}
Jayastu Senapati, Elias Jabbour, Nicholas J Short, Nitin Jain, Fadi Haddad, Tharakeswara Bathala, Iuliia Kovalenko, Aram Bidikian, Farhad Ravandi, Issa Khouri, Tapan M Kadia, Rebecca Garris, Guillermo Montalban Bravo, Kelly Chien, Elizabeth Shpall, Partow Kebriaei, Hagop M Kantarjian
{"title":"Liver elastography for risk-assessment of liver toxicity and risk factors for Sinusoidal obstruction syndrome in patients with acute lymphoblastic leukemia receiving inotuzumab ozogamicin.","authors":"Jayastu Senapati, Elias Jabbour, Nicholas J Short, Nitin Jain, Fadi Haddad, Tharakeswara Bathala, Iuliia Kovalenko, Aram Bidikian, Farhad Ravandi, Issa Khouri, Tapan M Kadia, Rebecca Garris, Guillermo Montalban Bravo, Kelly Chien, Elizabeth Shpall, Partow Kebriaei, Hagop M Kantarjian","doi":"10.1038/s41408-024-01098-4","DOIUrl":"10.1038/s41408-024-01098-4","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"14 1","pages":"129"},"PeriodicalIF":12.9,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11306742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900833","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}
J Martinez-Lopez, N Lopez-Muñoz, A Chari, S Dorado, S Barrio, S Arora, A Kumar, A Chung, T Martin, J Wolf
{"title":"Measurable residual disease (MRD) dynamics in multiple myeloma and the influence of clonal diversity analyzed by artificial intelligence.","authors":"J Martinez-Lopez, N Lopez-Muñoz, A Chari, S Dorado, S Barrio, S Arora, A Kumar, A Chung, T Martin, J Wolf","doi":"10.1038/s41408-024-01102-x","DOIUrl":"10.1038/s41408-024-01102-x","url":null,"abstract":"<p><p>Minimal residual disease (MRD) assessment is a known surrogate marker for survival in multiple myeloma (MM). Here, we present a single institution's experience assessing MRD by NGS of Ig genes and the long-term impact of depth of response as well as clonal diversity on the clinical outcome of a large population of MM patients; 482 MM patients at the University of California, San Francisco (UCSF) diagnosed from 2008 to 2020 were analyzed retrospectively. MRD assessment was performed by NGS. PFS curves were plotted by the Kaplan-Meier method. In the newly diagnosed group, 119 of 304, achieved MRD negativity at the level of 10<sup>-6</sup> at least once. These patients had a prolonged PFS versus patients who were persistently MRD positive at different levels (p > 0.0001). In the relapsed disease group, 64 of 178 achieved MRD negativity at 10<sup>-6</sup>, and PFS was prolonged versus patients who remained MRD positive (p = 0.03). Three categories of MRD dynamics were defined by artificial intelligence: (A) patients with ≥3 consistently MRD negative samples, (B) patients with continuously declining but detectable clones, and (C) patients with either increasing or a stable number of clones. Groups A and B had a more prolonged PFS than group C (p < 10<sup>-7</sup>). Patients who were MRD positive and had not yet relapsed had a higher clonal diversity than those patients who were MRD positive and had relapsed. MRD dynamics can accurately predict disease evolution and drive clinical decision-making. Clonal Diversity could complement MRD assessment in the prediction of outcomes in MM.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"14 1","pages":"131"},"PeriodicalIF":12.9,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11306767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900834","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}
Lukas Schloesser, Karin U Loeffler, Annkristin Heine, Frank G Holz, Martina C Herwig-Carl
{"title":"Dynamics of microcyst-like epithelial changes associated with Belantamab mafodotin therapy in a patient with multiple myeloma-a case report.","authors":"Lukas Schloesser, Karin U Loeffler, Annkristin Heine, Frank G Holz, Martina C Herwig-Carl","doi":"10.1038/s41408-024-01110-x","DOIUrl":"10.1038/s41408-024-01110-x","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"14 1","pages":"133"},"PeriodicalIF":12.9,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11306733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900830","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}
Victoria Shelton, Rajesh Detroja, Ting Liu, Keren Isaev, Anjali Silva, Verena Passerini, Mehran Bakhtiari, Lourdes Calvente, Michael Hong, Michael Y He, Saloni Modi, Samantha A Hershenfeld, Maja Ludvigsen, Charlotte Madsen, Stephen Hamilton-Dutoit, Francesco Annibale d'Amore, Marianne Brodtkorb, Nathalie A Johnson, Tara Baetz, David LeBrun, Josh W D Tobin, Maher K Gandhi, Andrew J Mungall, Wei Xu, Susana Ben-Neriah, Christian Steidl, Jan Delabie, Rosemarie Tremblay-LeMay, Opeyemi Jegede, Oliver Weigert, Brad Kahl, Andrew M Evens, Robert Kridel
{"title":"Identification of genetic subtypes in follicular lymphoma.","authors":"Victoria Shelton, Rajesh Detroja, Ting Liu, Keren Isaev, Anjali Silva, Verena Passerini, Mehran Bakhtiari, Lourdes Calvente, Michael Hong, Michael Y He, Saloni Modi, Samantha A Hershenfeld, Maja Ludvigsen, Charlotte Madsen, Stephen Hamilton-Dutoit, Francesco Annibale d'Amore, Marianne Brodtkorb, Nathalie A Johnson, Tara Baetz, David LeBrun, Josh W D Tobin, Maher K Gandhi, Andrew J Mungall, Wei Xu, Susana Ben-Neriah, Christian Steidl, Jan Delabie, Rosemarie Tremblay-LeMay, Opeyemi Jegede, Oliver Weigert, Brad Kahl, Andrew M Evens, Robert Kridel","doi":"10.1038/s41408-024-01111-w","DOIUrl":"10.1038/s41408-024-01111-w","url":null,"abstract":"<p><p>Follicular lymphoma (FL) exhibits considerable variability in biological features and clinical trajectories across patients. To dissect the diversity of FL, we utilized a Bernoulli mixture model to identify genetic subtypes in 713 pre-treatment tumor tissue samples. Our analysis revealed the existence of five subtypes with unique genetic profiles that correlated with clinicopathological characteristics. The clusters were enriched in specific mutations as follows: CS (CREBBP and STAT6), TT (TNFAIP3 and TP53), GM (GNA13 and MEF2B), Q (quiescent, for low mutation burden), and AR (mutations of mTOR pathway-related genes). The subtype Q was enriched for patients with stage I disease and associated with a lower proliferative history than the other subtypes. The AR subtype was unique in its enrichment for IgM-expressing FL cases and was associated with advanced-stage and more than 4 nodal sites. The existence of subtypes was validated in an independent cohort of 418 samples from the GALLIUM trial. Notably, patients assigned to the TT subtype consistently experienced inferior progression-free survival when treated with immunochemotherapy. Our findings offer insight into core pathways distinctly linked with each FL cluster and are expected to be informative in the era of targeted therapies.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"14 1","pages":"128"},"PeriodicalIF":12.9,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11306633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900832","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}
Eleanor Frost, Jonathan N Hofmann, Wen-Yi Huang, Ashley A Frazer-Abel, Kevin D Deane, Sonja I Berndt
{"title":"Serum levels of B-cell activating factor are associated with a reduced risk of chronic lymphocytic leukemia.","authors":"Eleanor Frost, Jonathan N Hofmann, Wen-Yi Huang, Ashley A Frazer-Abel, Kevin D Deane, Sonja I Berndt","doi":"10.1038/s41408-024-01106-7","DOIUrl":"10.1038/s41408-024-01106-7","url":null,"abstract":"<p><strong>Impact: </strong>Immune dysregulation is thought to contribute to chronic lymphocytic leukemia (CLL) risk, but biological mechanisms are unclear. We discovered that increased serum levels of B-cell activating factor (BAFF), an important regulator of B-cell maturation, were associated with a decreased risk of CLL, even >10 years after blood draw. Our findings suggest that BAFF could be a useful biomarker to assess risk among individuals at high risk, such as those with monoclonal b-cell lymphocytosis.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"14 1","pages":"132"},"PeriodicalIF":12.9,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11306784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900835","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}
Marco G Raddi, Sara Bencini, Benedetta Peruzzi, Giorgio Mattiuz, Sven De Pourcq, Michele Tanturli, Nicolas Chapuis, Angela Consagra, Luca Rigodanza, Cristina Amato, Alessandro Sanna, Elena Tofacchi, Enrico Attardi, Sophie Park, Olivier Kosmider, Francesco Annunziato, Michaela Fontenay, Valeria Santini
{"title":"Flow cytometric analysis of erythroid precursors and mutational signatures of lower risk myelodysplastic syndromes identify responders to erythroid stimulating agents.","authors":"Marco G Raddi, Sara Bencini, Benedetta Peruzzi, Giorgio Mattiuz, Sven De Pourcq, Michele Tanturli, Nicolas Chapuis, Angela Consagra, Luca Rigodanza, Cristina Amato, Alessandro Sanna, Elena Tofacchi, Enrico Attardi, Sophie Park, Olivier Kosmider, Francesco Annunziato, Michaela Fontenay, Valeria Santini","doi":"10.1038/s41408-024-01112-9","DOIUrl":"10.1038/s41408-024-01112-9","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"14 1","pages":"127"},"PeriodicalIF":12.9,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11306215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900831","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}
Dragan Jevremovic, Min Shi, Pedro Horna, Gregory E Otteson, Michael M Timm, Linda B Baughn, Patricia T Greipp, Wilson I Gonsalves, Prashant Kapoor, Morie A Gertz, Moritz Binder, Francis K Buadi, Jiehao Zhou, Angela Dispenzieri, Taxiarchis Kourelis, Eli Muchtar, S Vincent Rajkumar, Shaji K Kumar, Horatiu Olteanu
{"title":"Real-life sensitivity of flow cytometry minimal residual disease assessment for plasma cell neoplasms.","authors":"Dragan Jevremovic, Min Shi, Pedro Horna, Gregory E Otteson, Michael M Timm, Linda B Baughn, Patricia T Greipp, Wilson I Gonsalves, Prashant Kapoor, Morie A Gertz, Moritz Binder, Francis K Buadi, Jiehao Zhou, Angela Dispenzieri, Taxiarchis Kourelis, Eli Muchtar, S Vincent Rajkumar, Shaji K Kumar, Horatiu Olteanu","doi":"10.1038/s41408-024-01113-8","DOIUrl":"10.1038/s41408-024-01113-8","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"14 1","pages":"126"},"PeriodicalIF":12.9,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11291477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141858971","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}
Alex Wonnaparhown, Talal Hilal, Jacqueline Squire, Catherine Freeman, Rafael Fonseca
{"title":"IgG replacement in multiple myeloma","authors":"Alex Wonnaparhown, Talal Hilal, Jacqueline Squire, Catherine Freeman, Rafael Fonseca","doi":"10.1038/s41408-024-01107-6","DOIUrl":"https://doi.org/10.1038/s41408-024-01107-6","url":null,"abstract":"<p>T cell engagers (TCE) such as chimeric antigen receptor (CAR) T cell therapy and bispecific antibodies (BiAbs) for the treatment of multiple myeloma (MM) have significantly improved clinical outcomes, but have also raised awareness for ensuing post-treatment secondary immunodeficiency and hypogammaglobulinemia (HG). As patients with MM live longer, recurrent infections become a significant component of therapy-associated morbidity and mortality. Treatment of HG with immunoglobulin G replacement therapy (IgG-RT) has been a mainstay of the primary immunodeficiency (PI) world, and extrapolation to MM has recently started to show promising clinical outcomes. However, IgG-RT initiation, dosing, route, timing, monitoring, and management in MM has not been standardized in the setting of TCE. Progress in MM treatment will involve greater recognition and screening of underlying secondary immunodeficiency, identification of risk-stratification markers, optimizing IgG-RT management, and implementing other approaches to decrease the risk of infection. In this review, we summarize infection risk, risk of HG, and management strategies for IgG-RT in patients with relapsed MM after TCE.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"24 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141754725","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}
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