Pub Date : 2025-10-27DOI: 10.1038/s41375-025-02759-4
Mouhamad Khouja, Britta Kehden, Derek Blair, Christian Kuffer, Steve Wagner, Tim Versteegen, Philipp Nakov, Monika Brüggemann, Claudia Baldus, David Belada, Grzegorz S. Nowakowski, Anke Schilhabel, Nikos Darzentas, Christiane Pott, on behalf of the EuroClonality-NGS Working Group
The firstMIND trial (NCT04134936) evaluated the safety and efficacy of adding lenalidomide to R-CHOP+tafasitamab in the first-line treatment settings of patients with diffuse large B-cell lymphoma. To address response dynamics and the impact of measurable residual disease (MRD), we analyzed prospectively collected plasma samples from 56 study patients using the EuroClonality immunoglobulin gene (IG)-NGS assay. At baseline, disease-related clonotypes were identified in 50/56 (89%) patients by IG-NGS in cell-free (cf)DNA and/or FFPE samples. MRD markers were successfully identified in 49/52 (94%) cfDNA samples and 35/41 (85%) FFPE samples. Baseline cfDNA and circulating tumor (ct)DNA levels correlated with preclinical risk factors, and high cfDNA levels ≥3.35 log10hGE/ml plasma were significantly associated with poor progression-free survival (PFS) (hazard ratio (HR): 3.1). ctDNA clearance was rapid with 52% of patients MRD-negative at C2D1, 83% patients at C4D1, and 82% patients after finishing six 21-day cycles (end of treatment (EOT)) and a sustained treatment response (93% MRD negative) six months after EOT. ctDNA detection was associated with worse PFS outcomes at C2D1 (p = 0.039, HR:4.51, 95%Cl:0.93–21.74), C4D1 (p = 0.07, HR:3.34, 95%Cl:0.83–13.48) and EOT (p = 0.01, HR:6.38, 95%Cl:1.27–32.01) and inferior overall survival at these time points. In PET-positive patients, ctDNA-MRD had a higher specificity rendering PET/CT more precisely.
{"title":"ctDNA dynamics demonstrates rapid treatment response to tafasitamab + R-CHOP +/− lenalidomide and predicts outcome in diffuse large B-cell lymphoma: results from the phase 1b First-MIND study","authors":"Mouhamad Khouja, Britta Kehden, Derek Blair, Christian Kuffer, Steve Wagner, Tim Versteegen, Philipp Nakov, Monika Brüggemann, Claudia Baldus, David Belada, Grzegorz S. Nowakowski, Anke Schilhabel, Nikos Darzentas, Christiane Pott, on behalf of the EuroClonality-NGS Working Group","doi":"10.1038/s41375-025-02759-4","DOIUrl":"10.1038/s41375-025-02759-4","url":null,"abstract":"The firstMIND trial (NCT04134936) evaluated the safety and efficacy of adding lenalidomide to R-CHOP+tafasitamab in the first-line treatment settings of patients with diffuse large B-cell lymphoma. To address response dynamics and the impact of measurable residual disease (MRD), we analyzed prospectively collected plasma samples from 56 study patients using the EuroClonality immunoglobulin gene (IG)-NGS assay. At baseline, disease-related clonotypes were identified in 50/56 (89%) patients by IG-NGS in cell-free (cf)DNA and/or FFPE samples. MRD markers were successfully identified in 49/52 (94%) cfDNA samples and 35/41 (85%) FFPE samples. Baseline cfDNA and circulating tumor (ct)DNA levels correlated with preclinical risk factors, and high cfDNA levels ≥3.35 log10hGE/ml plasma were significantly associated with poor progression-free survival (PFS) (hazard ratio (HR): 3.1). ctDNA clearance was rapid with 52% of patients MRD-negative at C2D1, 83% patients at C4D1, and 82% patients after finishing six 21-day cycles (end of treatment (EOT)) and a sustained treatment response (93% MRD negative) six months after EOT. ctDNA detection was associated with worse PFS outcomes at C2D1 (p = 0.039, HR:4.51, 95%Cl:0.93–21.74), C4D1 (p = 0.07, HR:3.34, 95%Cl:0.83–13.48) and EOT (p = 0.01, HR:6.38, 95%Cl:1.27–32.01) and inferior overall survival at these time points. In PET-positive patients, ctDNA-MRD had a higher specificity rendering PET/CT more precisely.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"40 1","pages":"87-94"},"PeriodicalIF":13.4,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41375-025-02759-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373962","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}
Pub Date : 2025-10-27DOI: 10.1038/s41375-025-02789-y
Atte Nikkilä, Olli Lohi, Jonas Abrahamsson, Laimonas Griskevicius, Helene Hallböök, Ólafur Gísli Jónsson, Bendik Lund, Hanne Vibeke Marquart, Ulrik Overgaard, Katrin Palk, Kaie Pruunsild, Petter Quist-Paulsen, Nina Toft, Goda Elizabeta Vaitkeviciene, Ulla Wartiovaara-Kautto, Mats Heyman, Kim Vettenranta, Kjeld Schmiegelow
{"title":"Intensive chemotherapy for high-risk acute lymphoblastic leukemia in first remission: results from the NOPHO ALL2008 study","authors":"Atte Nikkilä, Olli Lohi, Jonas Abrahamsson, Laimonas Griskevicius, Helene Hallböök, Ólafur Gísli Jónsson, Bendik Lund, Hanne Vibeke Marquart, Ulrik Overgaard, Katrin Palk, Kaie Pruunsild, Petter Quist-Paulsen, Nina Toft, Goda Elizabeta Vaitkeviciene, Ulla Wartiovaara-Kautto, Mats Heyman, Kim Vettenranta, Kjeld Schmiegelow","doi":"10.1038/s41375-025-02789-y","DOIUrl":"10.1038/s41375-025-02789-y","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"40 1","pages":"215-218"},"PeriodicalIF":13.4,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41375-025-02789-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373960","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":"Structure-based prediction reveals a difference in the binding mode of anti-BCMA antibodies to BCMA and soluble BCMA","authors":"Jiro Kikuchi, Naoki Osada, Sae Matsuoka, Hiroshi Yasui, Yusuke Furukawa, Hideki Nakasone","doi":"10.1038/s41375-025-02792-3","DOIUrl":"10.1038/s41375-025-02792-3","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"40 1","pages":"211-214"},"PeriodicalIF":13.4,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145357898","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}
Pub Date : 2025-10-17DOI: 10.1038/s41375-025-02788-z
Thi Thanh Vu, Friedrich Stölzel, Kristy W. Wang, Christoph Röllig, Melinda L. Tursky, Timothy J. Molloy, David D. Ma
{"title":"Correction: miR-10a as a therapeutic target and predictive biomarker for MDM2 inhibition in acute myeloid leukemia","authors":"Thi Thanh Vu, Friedrich Stölzel, Kristy W. Wang, Christoph Röllig, Melinda L. Tursky, Timothy J. Molloy, David D. Ma","doi":"10.1038/s41375-025-02788-z","DOIUrl":"10.1038/s41375-025-02788-z","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 12","pages":"3059-3059"},"PeriodicalIF":13.4,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41375-025-02788-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313134","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}
Pub Date : 2025-10-17DOI: 10.1038/s41375-025-02779-0
Sarah J. Goodman, Darci T. Butcher, Sharon L. Guger, Eric Diehl, Jack Brzezinski, Brenda Spiegler, Brian J. Nieman, Prajkta Kallurkar, Aubrée Boulet Craig, Maja Krajinovic, Julie Laniel, Caroline Laverdière, Daniel Sinnett, Sarah Lippé, Andrei Turinsky, Mary Shago, Lisa J. Strug, Shinya Ito, Johann K. Hitzler, Russell Schachar, Rosanna Weksberg
{"title":"DNA methylation alterations in acute lymphoblastic leukemia survivors with late neurocognitive deficits","authors":"Sarah J. Goodman, Darci T. Butcher, Sharon L. Guger, Eric Diehl, Jack Brzezinski, Brenda Spiegler, Brian J. Nieman, Prajkta Kallurkar, Aubrée Boulet Craig, Maja Krajinovic, Julie Laniel, Caroline Laverdière, Daniel Sinnett, Sarah Lippé, Andrei Turinsky, Mary Shago, Lisa J. Strug, Shinya Ito, Johann K. Hitzler, Russell Schachar, Rosanna Weksberg","doi":"10.1038/s41375-025-02779-0","DOIUrl":"10.1038/s41375-025-02779-0","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 12","pages":"3042-3046"},"PeriodicalIF":13.4,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41375-025-02779-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311205","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}
Pub Date : 2025-10-15DOI: 10.1038/s41375-025-02783-4
D. Saul, C. Lischer, H. Bruns, N. Ziegler, A. Kannt, M. Michel, D. Mougiakakos
{"title":"OGG1 activation improves T cell resilience to oxidative stress after allo-SCT and T cell engager exposure","authors":"D. Saul, C. Lischer, H. Bruns, N. Ziegler, A. Kannt, M. Michel, D. Mougiakakos","doi":"10.1038/s41375-025-02783-4","DOIUrl":"10.1038/s41375-025-02783-4","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 12","pages":"3037-3041"},"PeriodicalIF":13.4,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41375-025-02783-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145296166","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}
Pub Date : 2025-10-13DOI: 10.1038/s41375-025-02754-9
Rachel B. Salit, Elizabeth O. Hexner, Nico Gagelmann, Nicolaus Kröger, Donal P. McLornan, Tania Jain, Vikas Gupta, Gabriela S. Hobbs, Roni Tamari, Marie Robin, Bart Scott, Wael Saber
{"title":"Defining remission following hematopoietic cell transplant for myelofibrosis: an international expert panel consensus","authors":"Rachel B. Salit, Elizabeth O. Hexner, Nico Gagelmann, Nicolaus Kröger, Donal P. McLornan, Tania Jain, Vikas Gupta, Gabriela S. Hobbs, Roni Tamari, Marie Robin, Bart Scott, Wael Saber","doi":"10.1038/s41375-025-02754-9","DOIUrl":"10.1038/s41375-025-02754-9","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 12","pages":"2862-2865"},"PeriodicalIF":13.4,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283329","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}
Pub Date : 2025-10-13DOI: 10.1038/s41375-025-02784-3
E. Rodríguez-Arbolí, R. P. Gale
{"title":"Does everyone with newly-diagnosed, untreated acute myeloid leukaemia need remission-induction chemotherapy before advancing to a transplant?","authors":"E. Rodríguez-Arbolí, R. P. Gale","doi":"10.1038/s41375-025-02784-3","DOIUrl":"10.1038/s41375-025-02784-3","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 12","pages":"2858-2861"},"PeriodicalIF":13.4,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283375","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}
Pub Date : 2025-10-10DOI: 10.1038/s41375-025-02753-w
Jesse Geels, Anna van Rhenen, Patrycja Gradowska, Folkert W. Asselbergs, Marijke Linschoten
Patients with acute myeloid leukemia (AML) are at increased risk of cardiovascular disease, particularly heart failure. Anthracyclines are integral to remission induction therapy in patients eligible for intensive treatment and well-known for their association with cardiotoxicity. However, the incidence of heart failure and other cardiovascular adverse events (CVAEs), as well as differences across various anthracycline agents, has not been comprehensively assessed. We systematically searched PubMed and EMBASE for studies conducted in AML patients treated with anthracyclines during remission induction. Forty-one studies (5995 patients), primarily clinical trials, published between February 1991 and March 2024 were included. The pooled proportion of heart failure was 3.2% (95% CI 1.0–6.2) overall and 2.3% (95% CI 1.4–3.3), 5.0% (95% CI 0.3–14.1) and 10.2% (95% CI 2.4–21.7) for patients treated with daunorubicin, idarubicin or mitoxantrone respectively. Cardiac function was infrequently monitored, and CVAE reporting was generally poor. Since current adverse event grading systems primarily rely on clinical symptoms to assign severity, significant asymptomatic declines in cardiac function will remain undetected. Enhanced CVAE monitoring and reporting, along with revisions to established grading systems, is needed to better identify subclinical cardiotoxicity in AML patients, enabling timely intervention to prevent progression to more advanced heart failure stages.
急性髓性白血病（AML）患者患心血管疾病的风险增加，尤其是心力衰竭。蒽环类药物是有资格接受强化治疗的患者缓解诱导治疗不可或缺的一部分，并因其与心脏毒性相关而闻名。然而，心衰和其他心血管不良事件（CVAEs）的发生率以及各种蒽环类药物之间的差异尚未得到全面评估。我们系统地检索了PubMed和EMBASE中在诱导缓解期间接受蒽环类药物治疗的AML患者中进行的研究。纳入1991年2月至2024年3月期间发表的41项研究（5995名患者），主要是临床试验。总的来说，心力衰竭的合并比例为3.2% (95% CI 1.0-6.2)，而接受柔红霉素、依甲红霉素或米托沙酮治疗的患者心力衰竭的合并比例分别为2.3% （95% CI 1.4-3.3）、5.0% （95% CI 0.3-14.1）和10.2% （95% CI 2.4-21.7）。很少监测心功能，CVAE报告普遍较差。由于目前的不良事件分级系统主要依赖于临床症状来分配严重程度，因此心功能的显著无症状下降仍未被发现。需要加强CVAE监测和报告，同时修订现有的分级系统，以更好地识别AML患者的亚临床心脏毒性，使及时干预能够防止进展到更晚期的心力衰竭阶段。
{"title":"Heart failure in patients with acute myeloid leukemia (AML) treated with anthracycline agents during remission induction therapy: a systematic review and meta-analysis","authors":"Jesse Geels, Anna van Rhenen, Patrycja Gradowska, Folkert W. Asselbergs, Marijke Linschoten","doi":"10.1038/s41375-025-02753-w","DOIUrl":"10.1038/s41375-025-02753-w","url":null,"abstract":"Patients with acute myeloid leukemia (AML) are at increased risk of cardiovascular disease, particularly heart failure. Anthracyclines are integral to remission induction therapy in patients eligible for intensive treatment and well-known for their association with cardiotoxicity. However, the incidence of heart failure and other cardiovascular adverse events (CVAEs), as well as differences across various anthracycline agents, has not been comprehensively assessed. We systematically searched PubMed and EMBASE for studies conducted in AML patients treated with anthracyclines during remission induction. Forty-one studies (5995 patients), primarily clinical trials, published between February 1991 and March 2024 were included. The pooled proportion of heart failure was 3.2% (95% CI 1.0–6.2) overall and 2.3% (95% CI 1.4–3.3), 5.0% (95% CI 0.3–14.1) and 10.2% (95% CI 2.4–21.7) for patients treated with daunorubicin, idarubicin or mitoxantrone respectively. Cardiac function was infrequently monitored, and CVAE reporting was generally poor. Since current adverse event grading systems primarily rely on clinical symptoms to assign severity, significant asymptomatic declines in cardiac function will remain undetected. Enhanced CVAE monitoring and reporting, along with revisions to established grading systems, is needed to better identify subclinical cardiotoxicity in AML patients, enabling timely intervention to prevent progression to more advanced heart failure stages.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"40 1","pages":"120-129"},"PeriodicalIF":13.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261390","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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