Hamlet Gasoyan, Faiz Anwer, Jeffrey D. Kovach, Nicholas J. Casacchia, Ming Wang, Jason Valent, Michael T. Halpern, Michael B. Rothberg
{"title":"Disparities in time to treatment with oral antimyeloma medications","authors":"Hamlet Gasoyan, Faiz Anwer, Jeffrey D. Kovach, Nicholas J. Casacchia, Ming Wang, Jason Valent, Michael T. Halpern, Michael B. Rothberg","doi":"10.1038/s41408-024-01128-1","DOIUrl":"https://doi.org/10.1038/s41408-024-01128-1","url":null,"abstract":"<p>This retrospective cohort study used Taussig Cancer Center’s Myeloma Patient Registry to identify adults with multiple myeloma diagnosed between January 2017-December 2021. Electronic health records data captured time from diagnosis to initial prescription fill for oral antimyeloma medications and initiation of facility administered or oral antimyeloma treatment. We identified 720 patients with a mean age at diagnosis of 67 years ±11; 55% were male, 77% White, 22% Black, 1% other races, covered by private insurance (36%), traditional Medicare (29%), Medicare Advantage (25%), and Medicaid (8.3%). Over a third of patients (37%) resided in an area in the most disadvantaged area deprivation index (ADI) quartile. The median available follow-up was 765 days. Seventy-five percent of the cohort filled an oral antimyeloma medication prescription (excluding corticosteroids), with a median time to fill of 28 days (IQR, 15–61). In the multivariable Cox regression model, Black race (vs. White, adjusted hazard ratio [aHR], 0.61, 95% CI, 0.42–0.87), older age at diagnosis (aHR per 1 year, 0.97, 95% CI, 0.95–0.98), diagnosis during an inpatient admission (aHR, 0.63, 95% CI, 0.43–0.92), and estimated glomerular filtration rate ≤29 ml/min/1.73 m<sup>2</sup> (vs. ≥60, aHR, 0.46, 95% CI, 0.29–0.73) were negatively associated with prescription fill for oral antimyeloma medication at 30 days, while insurance type and ADI were not significant predictors.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"7 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142042632","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}
Gianluca Cavallaro, Anna Grassi, Chiara Pavoni, Maria Caterina Micò, Alessandro Busca, Irene Maria Cavattoni, Stella Santarone, Carlo Borghero, Attilio Olivieri, Giuseppe Milone, Patrizia Chiusolo, Pellegrino Musto, Riccardo Saccardi, Francesca Patriarca, Fabrizio Pane, Giorgia Saporiti, Paolo Rivela, Elisabetta Terruzzi, Raffaella Cerretti, Giuseppe Marotta, Angelo Michele Carella, Arnon Nagler, Domenico Russo, Paolo Corradini, Paolo Bernasconi, Anna Paola Iori, Luca Castagna, Nicola Mordini, Elena Oldani, Carmen Di Grazia, Andrea Bacigalupo, Alessandro Rambaldi
{"title":"Busulfan-fludarabine versus busulfan-cyclophosphamide for allogeneic transplant in acute myeloid leukemia: long term analysis of GITMO AML-R2 trial","authors":"Gianluca Cavallaro, Anna Grassi, Chiara Pavoni, Maria Caterina Micò, Alessandro Busca, Irene Maria Cavattoni, Stella Santarone, Carlo Borghero, Attilio Olivieri, Giuseppe Milone, Patrizia Chiusolo, Pellegrino Musto, Riccardo Saccardi, Francesca Patriarca, Fabrizio Pane, Giorgia Saporiti, Paolo Rivela, Elisabetta Terruzzi, Raffaella Cerretti, Giuseppe Marotta, Angelo Michele Carella, Arnon Nagler, Domenico Russo, Paolo Corradini, Paolo Bernasconi, Anna Paola Iori, Luca Castagna, Nicola Mordini, Elena Oldani, Carmen Di Grazia, Andrea Bacigalupo, Alessandro Rambaldi","doi":"10.1038/s41408-024-01116-5","DOIUrl":"https://doi.org/10.1038/s41408-024-01116-5","url":null,"abstract":"<p>We report the long-term results of a randomized trial (GITMO, AML-R2), comparing 1:1 the combination of busulfan and cyclophosphamide (BuCy2, <i>n</i> = 125) and the combination of busulfan and fludarabine (BuFlu, <i>n</i> = 127) as conditioning regimen in acute myeloid leukemia patients (median age 51 years, range 40–65) undergoing allogeneic hematopoietic stem cell transplantation. With a median follow-up of 6 years, significantly better non-relapse mortality (NRM) was confirmed in BuFlu recipients, which is sustained up to 4 years after transplant (10% vs. 20%, <i>p</i> = 0.0388). This difference was higher in patients older than 51 years (11% in BuFlu vs. 27% in BuCy2, <i>p</i> = 0.0262). The cumulative incidence of relapse, which was the first cause of death in the entire study population, did not differ between the two randomized arms. Similarly, the leukemia-free survival (LFS) and overall survival (OS) were not different in the two cohorts, even when stratifying patients per median age. Graft-and relapse-free survival (GRFS) in BuFlu arm vs. the BuCy2 arm was 25% vs. 20% at 4 years and 20% vs. 17% at 10 years. Hence, the benefit gained by NRM reduction is not offsets by an increased relapse. Leukemia relapse remains a major concern, urging the development of new therapeutic approaches.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"1 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142013835","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}
Hauke Thomsen, Subhayan Chattopadhyay, Niels Weinhold, Pavel Vodicka, Ludmila Vodickova, Per Hoffmann, Markus M. Nöthen, Karl-Heinz Jöckel, Börge Schmidt, Roman Hajek, Göran Hallmans, Ulrika Pettersson-Kymmer, Florentin Späth, Hartmut Goldschmidt, Kari Hemminki, Asta Försti
{"title":"Haplotype analysis identifies functional elements in monoclonal gammopathy of unknown significance","authors":"Hauke Thomsen, Subhayan Chattopadhyay, Niels Weinhold, Pavel Vodicka, Ludmila Vodickova, Per Hoffmann, Markus M. Nöthen, Karl-Heinz Jöckel, Börge Schmidt, Roman Hajek, Göran Hallmans, Ulrika Pettersson-Kymmer, Florentin Späth, Hartmut Goldschmidt, Kari Hemminki, Asta Försti","doi":"10.1038/s41408-024-01121-8","DOIUrl":"https://doi.org/10.1038/s41408-024-01121-8","url":null,"abstract":"<p>Genome-wide association studies (GWASs) based on common single nucleotide polymorphisms (SNPs) have identified several loci associated with the risk of monoclonal gammopathy of unknown significance (MGUS), a precursor condition for multiple myeloma (MM). We hypothesized that analyzing haplotypes might be more useful than analyzing individual SNPs, as it could identify functional chromosomal units that collectively contribute to MGUS risk. To test this hypothesis, we used data from our previous GWAS on 992 MGUS cases and 2910 controls from three European populations. We identified 23 haplotypes that were associated with the risk of MGUS at the genome-wide significance level (<i>p</i> < 5 × 10<sup>−8</sup>) and showed consistent results among all three populations. In 10 genomic regions, strong promoter, enhancer and regulatory element-related histone marks and their connections to target genes as well as genome segmentation data supported the importance of these regions in MGUS susceptibility. Several associated haplotypes affected pathways important for MM cell survival such as ubiquitin-proteasome system (<i>RNF186</i>, <i>OTUD3</i>), PI3K/AKT/mTOR (<i>HINT3</i>), innate immunity (<i>SEC14L1</i>, <i>ZBP1</i>), cell death regulation (<i>BID</i>) and NOTCH signaling (<i>RBPJ</i>). These pathways are important current therapeutic targets for MM, which may highlight the advantage of the haplotype approach homing to functional units.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"10 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142007638","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}
Noora Hannuksela, Anu Partanen, Anna Anttalainen, Liisa Ukkola-Vuoti, Iiro Toppila, Johanna Vikkula, Katja Marin, Hanne Kuitunen, Tatu Miettinen, Outi Kuittinen, Aino Rönkä
{"title":"Survival of patients with classical Hodgkin lymphoma in Finland: a national population-based analysis","authors":"Noora Hannuksela, Anu Partanen, Anna Anttalainen, Liisa Ukkola-Vuoti, Iiro Toppila, Johanna Vikkula, Katja Marin, Hanne Kuitunen, Tatu Miettinen, Outi Kuittinen, Aino Rönkä","doi":"10.1038/s41408-024-01125-4","DOIUrl":"https://doi.org/10.1038/s41408-024-01125-4","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"54 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142007634","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}
Judith Lind, Osman Aksoy, Michaela Prchal-Murphy, Fengjuan Fan, Mariateresa Fulciniti, Dagmar Stoiber, Latifa Bakiri, Erwin F. Wagner, Elisabeth Zwickl-Traxler, Martin Sattler, Karoline Kollmann, Sonia Vallet, Klaus Podar
{"title":"Dual therapeutic targeting of MYC and JUNB transcriptional programs for enhanced anti-myeloma activity","authors":"Judith Lind, Osman Aksoy, Michaela Prchal-Murphy, Fengjuan Fan, Mariateresa Fulciniti, Dagmar Stoiber, Latifa Bakiri, Erwin F. Wagner, Elisabeth Zwickl-Traxler, Martin Sattler, Karoline Kollmann, Sonia Vallet, Klaus Podar","doi":"10.1038/s41408-024-01117-4","DOIUrl":"https://doi.org/10.1038/s41408-024-01117-4","url":null,"abstract":"<p>Deregulation of transcription factors (TFs) leading to uncontrolled proliferation of tumor cells within the microenvironment represents a hallmark of cancer. However, the biological and clinical impact of transcriptional interference, particularly in multiple myeloma (MM) cells, remains poorly understood. The present study shows for the first time that MYC and JUNB, two crucial TFs implicated in MM pathogenesis, orchestrate distinct transcriptional programs. Specifically, our data revealed that expression levels of MYC, JUNB, and their respective downstream targets do not correlate and that their global chromatin-binding patterns are not significantly overlapping. Mechanistically, MYC expression was not affected by JUNB knockdown, and conversely, JUNB expression and transcriptional activity were not affected by MYC knockdown. Moreover, suppression of MYC levels in MM cells <i>via</i> targeting the master regulator BRD4 by either siRNA-mediated knockdown or treatment with the novel <i>proteolysis targeting chimera</i> (PROTAC) MZ-1 overcame bone marrow (BM) stroma cell/IL-6-induced MYC- but not MEK-dependent JUNB-upregulation and transcriptional activity. Consequently, targeting of the two non-overlapping MYC- and JUNB-transcriptoms by MZ-1 in combination with genetic or pharmacological JUNB-targeting approaches synergistically enhanced MM cell death, both in 2D and our novel dynamic 3D models of the BM milieu as well as in murine xenografts. In summary, our data emphasize the opportunity to employ MYC and JUNB dual-targeting treatment strategies in MM as another exciting approach to further improve patient outcomes.</p><figure></figure>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"9 7 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142002764","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}
Charlotte Pawlyn, Fredrik H. Schjesvold, David A. Cairns, L. J. Wei, Faith Davies, Omar Nadeem, Haifaa Abdulhaq, Maria-Victoria Mateos, Jacob Laubach, Katja Weisel, Heinz Ludwig, S. Vincent Rajkumar, Pieter Sonneveld, Graham Jackson, Gareth Morgan, Paul G. Richardson
{"title":"Progression-free survival as a surrogate endpoint in myeloma clinical trials: an evolving paradigm","authors":"Charlotte Pawlyn, Fredrik H. Schjesvold, David A. Cairns, L. J. Wei, Faith Davies, Omar Nadeem, Haifaa Abdulhaq, Maria-Victoria Mateos, Jacob Laubach, Katja Weisel, Heinz Ludwig, S. Vincent Rajkumar, Pieter Sonneveld, Graham Jackson, Gareth Morgan, Paul G. Richardson","doi":"10.1038/s41408-024-01109-4","DOIUrl":"https://doi.org/10.1038/s41408-024-01109-4","url":null,"abstract":"<p>Measurement of overall survival (OS) remains the gold standard for interpreting the impact of new therapies for multiple myeloma in phase 3 trials. However, as outcomes have improved, it is increasingly challenging to use OS as the primary endpoint if timely approval of novel agents is to be ensured to enable maximum benefit for patients. Surrogate endpoints of OS, such as progression-free survival (PFS) and response to treatment, have contributed to approval decisions by the Food and Drug Administration (FDA) and European Medicines Agency as endpoints demonstrating clinical benefit, and the FDA has recently supported the use of minimal residual disease (MRD) as an accelerated approval endpoint in multiple myeloma. This review aims to address situations in which the use of PFS as a surrogate endpoint warrants careful interpretation especially for specific subgroups of patients and considers ways to ensure that studies can be designed to account for possible discordance between PFS and OS. The utility of subgroup analyses, including the potential for those not pre-specified, to identify target populations for new agents is also discussed.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"21 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918919","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}
Arushi Khurana, Allison C Rosenthal, Razan Mohty, Mamatha Gaddam, Radhika Bansal, Matthew A Hathcock, Adrienne N Nedved, Urshila Durani, Madiha Iqbal, Yucai Wang, Jonas Paludo, J C Villasboas, David Dingli, Taxiarchis Kourelis, Nelson Leung, Hassan Alkhateeb, Michael W Ruff, Alice Gallo de Moraes, Paschalis Vergidis, Joerg Herrmann, Saad S Kenderian, N Nora Bennani, Patrick B Johnston, Stephen M Ansell, Yi Lin
{"title":"Chimeric antigen receptor T-cell therapy associated hemophagocytic lymphohistiocytosis syndrome: clinical presentation, outcomes, and management.","authors":"Arushi Khurana, Allison C Rosenthal, Razan Mohty, Mamatha Gaddam, Radhika Bansal, Matthew A Hathcock, Adrienne N Nedved, Urshila Durani, Madiha Iqbal, Yucai Wang, Jonas Paludo, J C Villasboas, David Dingli, Taxiarchis Kourelis, Nelson Leung, Hassan Alkhateeb, Michael W Ruff, Alice Gallo de Moraes, Paschalis Vergidis, Joerg Herrmann, Saad S Kenderian, N Nora Bennani, Patrick B Johnston, Stephen M Ansell, Yi Lin","doi":"10.1038/s41408-024-01119-2","DOIUrl":"10.1038/s41408-024-01119-2","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"14 1","pages":"136"},"PeriodicalIF":12.9,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11319601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970603","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 roadmap towards improving outcomes in multiple myeloma","authors":"Mohamad Mohty, Thierry Facon, Florent Malard, Jean-Luc Harousseau","doi":"10.1038/s41408-024-01115-6","DOIUrl":"https://doi.org/10.1038/s41408-024-01115-6","url":null,"abstract":"<p>Multiple myeloma (MM) is a chronic hematologic malignancy that remains incurable, because most patients eventually relapse or become refractory to current treatments. MM is a major health problem, with a globally increasing incidence. While, increase in the choice of MM treatment, including new immunotherapies (bispecific monoclonal antibodies and chimeric antigen receptor (CAR)-T cell therapy), may allow to further improve MM patients’ outcomes, some non-therapy-related key issues may represent a pre-requisite towards improving MM outcomes in the next few years. This includes, the necessity of real-world evidence data, of a better definition of frailty, of a dynamic disease risk assessment, of a better definition of high-risk disease, broader accessibility to novel drugs, and to ensure diversity and representation of underrepresented groups. These key issues will be discussed in the current perspective review.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"56 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918922","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}
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}
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