The Lancet Haematology最新文献

{"title":"IL-10-expressing, anti-CD19 CAR T cells for patients with relapsed or refractory B-cell acute lymphoblastic leukaemia: an open-label, single-arm, phase 1 study.","authors":"Qianwen Xu,Yugang Guo,Min Gao,Lei Xue,Hui Xu,Hui Li,Xuhan Zhang,Chongling Liu,Youjia Li,Qian Chen,Jingjing Ren,Karthik Sathiyanadan,Yongxian Hu,Li Tang,He Huang,Xingbing Wang","doi":"10.1016/s2352-3026(25)00253-4","DOIUrl":"https://doi.org/10.1016/s2352-3026(25)00253-4","url":null,"abstract":"BACKGROUNDAlthough chimeric antigen receptor (CAR) T-cell therapy has improved clinical outcomes for patients with relapsed or refractory B-cell acute lymphoblastic leukaemia, treatment resistance and relapse after remission driven by CAR T-cell dysfunction remain significant clinical challenges. To mitigate this limitation, we developed anti-CD19 CAR T cells expressing IL-10 (META 10-19) and aimed to assess their safety and activity in this patient group.METHODSWe conducted an open-label, single-arm, phase 1 study at the First Affiliated Hospital of University of Science and Technology of China, Hefei, China. Patients aged 3-70 years with relapsed or refractory B-cell acute lymphoblastic leukaemia diagnosed according to the 5th edition of WHO's Classification of Haematolymphoid Tumours and an Eastern Cooperative Oncology Group performance status score of 0-1 were eligible for inclusion. Lymphodepletion was achieved by use of intravenous fludarabine (25-30 mg/m2 per day) and intravenous cyclophosphamide (250-300 mg/m2 per day) from day -5 to -3. META 10-19 was administered intravenously in a single infusion of 0·1 × 106 or 0·2 × 106 CAR T cells per kg. The primary endpoints were safety, assessed by dose-limiting toxicity, immune effector cell-associated toxicity, and other treatment-related adverse events; and activity, assessed by clinical response rate and survival. Safety and activity were analysed in all eligible patients who received META 10-19 infusion. This study is registered with ClinicalTrials.gov, NCT05747157, and has been completed.FINDINGSBetween May 16, 2023, and July 29, 2024, 15 patients were enrolled and underwent whole-blood collection. 12 patients (median age 48 years [IQR 33-53]) received META 10-19 infusion and were included in the analyses, of whom all patients were Chinese, seven (58%) were men, and five (42%) were women. Median follow-up was 12·5 months (IQR 7·4-15·6). The most common grade 3 or worse adverse events were haematological toxicities in all 12 (100%) patients, including neutropenia (12 [100%]), anaemia (ten [83%]), and thrombocytopenia (ten [83%]). 11 (92%) patients had grade 1 or 2 cytokine release syndrome; no patients experienced immune effector cell-associated neurotoxicity syndrome. No treatment-related deaths were reported. Overall response at 1 month was observed in all 12 (100%) patients, with complete response in four (33%) patients, complete response with incomplete or partial haematological recovery in five (42%) patients, and morphological leukaemia-free state in three (25%) patients.INTERPRETATIONMETA 10-19 showed a manageable safety profile and promising antileukaemic activity in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia at low doses, highlighting that IL-10 engineering is a potential strategy for optimising CAR T-cell therapy in this patient group.FUNDINGCentre for Leading Medicine and Advanced Technologies of Institute of Health and Medicine, Hefei Comprehensive ","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytokine-engineered CAR T-cell therapy in relapsed or refractory B-cell acute lymphoblastic leukaemia.","authors":"Rawan G Faramand,Lori Muffly","doi":"10.1016/s2352-3026(25)00263-7","DOIUrl":"https://doi.org/10.1016/s2352-3026(25)00263-7","url":null,"abstract":"","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"134 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enasidenib plus venetoclax in patients with IDH2-mutated relapsed or refractory acute myeloid leukaemia or myelodysplastic syndrome (ENAVEN-AML): a multicentre, single-arm, phase 1b/2 trial.","authors":"Guillaume Richard-Carpentier,Gopila Gupta,Charina Koraksic,Severine Cathelin,Lisa Wang,Aniket Bankar,Marta Davidson,Vikas Gupta,Dawn Maze,Mark D Minden,Tracy Murphy,Aaron D Schimmer,Andre C Schuh,Hassan Sibai,Karen Yee,Courtney D DiNardo,Joseph Brandwein,Caroline J McNamara,Steven M Chan","doi":"10.1016/s2352-3026(25)00254-6","DOIUrl":"https://doi.org/10.1016/s2352-3026(25)00254-6","url":null,"abstract":"BACKGROUNDEnasidenib, a mutant IDH2 inhibitor, is used to treat IDH2-mutated acute myeloid leukaemia (AML). Preclinical studies have demonstrated synergy between enasidenib and venetoclax, a BCL2 inhibitor, in IDH2-mutated AML. The aim of this study was to evaluate the safety and activity of enasidenib plus venetoclax in patients with relapsed or refractory IDH2-mutated AML or myelodysplastic syndromes (MDS).METHODSThe ENAVEN-AML study was a single-arm, phase 1b/2 trial conducted at two centres in Canada. Patients were eligible to participate if they were 18 years or older, had an Eastern Cooperative Oncology Group performance status of 0 to 2, had a confirmed IDH2 mutation (affecting Arg140 or Arg172), and had AML or MDS that was refractory or had relapsed after at least one line of treatment. Patients were treated with venetoclax 400 mg orally daily with a 3-day dose ramp-up starting on cycle 1 day 1 and enasidenib 100 mg orally daily starting on cycle 1 day 15. The primary endpoint of the phase 1b portion was safety, which included dose-limiting toxicity and the frequency and severity of treatment-emergent adverse events (TEAEs), as well as determining the maximum tolerated dose and recommended phase 2 dose. The primary objective of the phase 2 portion was to assess preliminary activity, with overall response rate by intention-to-treat as the primary endpoint. Assessment of safety and activity were determined on the pooled analysis data from the phase 1 and 2 studies. The ENAVEN-AML study is registered with ClinicalTrials.gov (NCT04092179) and is completed.FINDINGSFrom Nov 12, 2020, to July 5, 2022, the study enrolled 27 patients (13 in phase 1b, 14 in phase 2) and the median follow-up was 20·2 months (IQR 15·0-23·0) at the data cutoff on Sept 30, 2023. The median age was 70 years (IQR 55-76); 16 (59%) of 27 patients were male, 11 (41%) female, and 19 (70%) White. 26 patients had relapsed or refractory AML, and one patient had relapsed MDS. The most common grade 3 or worse TEAEs were febrile neutropenia (n=11, 41%), infections (n=8, 30%), thrombocytopenia (n=7, 26%), pneumonia (n=6, 22%), sepsis (n=5, 19%), and anaemia (n=5, 19%). One case of IDH inhibitor-associated differentiation syndrome was observed. Serious adverse events were reported in 17 (62%) of 27 patients, most commonly infections (n=11, 41%) and intracranial bleeding (n=5, 19%). No dose-limiting toxicities or treatment-related deaths were observed. The recommended phase 2 dose was 400 mg daily for venetoclax and 100 mg daily for enasidenib. Of the 26 patients with AML, the overall response rate was 62% (95% CI 41-80; 16 of 26), with 13 (50%) of 26 having complete remission. The only patient with MDS did not respond to enasidenib plus venetoclax.INTERPRETATIONEnasidenib plus venetoclax is safe, with no unexpected TEAEs or treatment-related deaths, and shows preliminary activity in patients with relapsed or refractory IDH2-mutated AML and MDS.FUNDINGAbbVie and Bristol Myers Squibb.","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary thyroid diffuse large B-cell lymphoma in a teenager.","authors":"Baptiste Le Calvez,Stéphanie Mathis,Pierre Lemaire,Véronique Meignin,Thierry Leblanc,Laetitia Vercellino,Florian Chevillon","doi":"10.1016/s2352-3026(25)00233-9","DOIUrl":"https://doi.org/10.1016/s2352-3026(25)00233-9","url":null,"abstract":"","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"11 1","pages":"e850"},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GPRC5D-targeted CAR T-cell therapy (CT071) in patients with relapsed or refractory multiple myeloma: a first-in-human, single-centre, single-arm, phase 1 trial.","authors":"Lina Jin,Sinan Gu,Qianqi Ruan,Jing Lu,Wanting Qiang,Haiyan He,Xiaoqiang Fan,Jin Liu,Pei Guo,Xingxing Meng,Nishanthan Rajakumaraswamy,Deng Chen,Zonghai Li,Juan Du","doi":"10.1016/s2352-3026(25)00176-0","DOIUrl":"https://doi.org/10.1016/s2352-3026(25)00176-0","url":null,"abstract":"BACKGROUNDRelapsed or refractory multiple myeloma remains incurable. CT071 is a fully human, autologous, chimeric antigen receptor (CAR) T-cell therapy directed against G protein-coupled receptor class C group 5 member D (GPRC5D), with expedited manufacturing. This trial aimed to assess the preliminary activity, safety, and cellular kinetics of CT071 in relapsed or refractory multiple myeloma.METHODSThis first-in-human, single-centre, single-arm, phase 1 study was conducted in China at Shanghai Changzheng Hospital. Eligible patients were aged 18 years or older with relapsed or refractory multiple myeloma who had received three or more previous lines of therapy including a proteasome inhibitor and an immunomodulatory agent, or had double-class refractory therapy, and had progressive disease on the last line of therapy. Eastern Cooperative Oncology Group performance status 0-2 was required. Patients received CT071 at 0·1 × 106 CAR T cells per kg or 0·3 × 106 CAR T cells per kg. The primary endpoint was safety, which included dose-limiting toxicities, adverse events, and dose determination. Activity was also evaluated as a secondary endpoint. All patients receiving CT071 were included in the safety and activity analyses. This trial is registered with ClinicalTrials.gov (NCT05838131) and enrolment is complete.FINDINGSBetween April 28, 2023, and June 21, 2024, 23 patients were enrolled and underwent apheresis. Three patients were excluded after apheresis (one discontinued due to rapid disease progression, one due to active infection, and one was withdrawn because of failed manufacture of CAR T cells), thus 20 patients were infused. Median age was 63·0 years (IQR 53·0-65·5). 12 (60%) of 20 patients were male and eight (40%) were female; all patients were Chinese. Median follow-up was 10·71 months (IQR 6·13-12·02). No dose-limiting toxicities were observed, and the recommended phase 2 dose was determined at 0·1 × 106 CAR T cells per kg. Haematological toxicities were the most common grade 3 or worse treatment-related adverse events, occurring in all patients. Cytokine release syndrome occurred in 12 (60%) of 20 patients, all of which were grade 1-2. One (5%) patient had grade 3 immune effector cell-associated neurotoxicity syndrome. Serious treatment-related adverse events were reported in seven (35%) patients; no treatment-related deaths occurred. Skin-related events included onychomadesis reported in four (20%) patients and rash in one (5%) patient, all of which were grade 1. The objective response rate was 100% (95% CI 83·2-100), with a complete response or better rate of 50% (ten of 20 patients).INTERPRETATIONCT071 demonstrated an encouraging safety profile with compelling activity in patients with relapsed or refractory multiple myeloma.FUNDINGNational Natural Science Foundation of China and Clinical Research Plan of Shanghai Hospital Development Center.","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"82 1","pages":"e798-e807"},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence, mortality, and survival associated with acute leukaemia subtypes by age group in China: a population-based cancer registry analysis and cohort study.","authors":"Wei Yin,Xiaoyu Yan,Jiaoyang Cai,Bingfeng Han,Peng Yin,Gang Lu,Wenyan Cheng,Jianan Zhang,Huiyi Wu,Jiaqi Ren,Pengyu Ren,Zifang Zhou,Haibo Wang,Ying Shi,Lanxia Gan,Depei Wu,Jie Jin,Yongping Song,Zhongxing Jiang,Xiaojing Yan,Ting Niu,Yu Hu,Fei Li,Sujun Gao,Tao Cheng,Jianxiang Wang,Xi Zhang,Xiaojun Huang,Qifa Liu,Xiaoyu Zhu,Pengcheng He,Yuqing Chen,Tonghua Yang,Jianyong Li,Xudong Wei,Yongrong Lai,Jishi Wang,Jinsong Yan,Jie Yu,Xiaofan Zhu,Weiqun Xu,Yufeng Liu,Ju Gao,Hua Jiang,Yongzhi Zheng,Hua Wang,Yunyan He,Yongjun Fang,Shuhong Shen,Jing Chen,Bing Chen,Sujiang Zhang,Yang Shen,Jin Wang,Jianqing Mi,Weili Zhao,Hao Zhang,Maigeng Zhou,Wenqiang Wei,Jie He,Zhu Chen,Sai-Juan Chen, , ","doi":"10.1016/s2352-3026(25)00236-4","DOIUrl":"https://doi.org/10.1016/s2352-3026(25)00236-4","url":null,"abstract":"BACKGROUNDAcute leukaemia represents a crucial health challenge. However, nationwide data delineating the incidence of acute leukaemia subtypes, as well as mortality and survival outcomes, remain scarce in China. We aimed to provide a comprehensive assessment of the epidemiology of acute leukaemia subtypes across China.METHODSWe conducted a population-based cancer registry analysis and cohort study in China, by integrating data from five national databases through unique national identification numbers. The main outcomes were age-standardised rates (ASRs) for incidence and mortality and overall survival for acute leukaemia subtypes. Acute leukaemia incidence and mortality data in 2019 were extracted from National Cancer Centre (NCC) registries linked to the Hospital Quality Monitoring System (HQMS), stratified by age, sex, and region. ASRs were calculated with Segi's world standard population with 95% CIs across the general population. For the survival analysis, we established a cohort from the Chinese Childhood Leukaemia Registry (33 530 children aged 0-14 years) and National Adult Acute Leukaemia Registry of China (71 477 adults aged ≥15 years) for 2016-20, integrated with the Cause of Death Reporting System and HQMS. Patients were stratified by subtype, age, sex, region, molecular characteristics, treatment modalities, and diagnosis period (2016-18 vs 2019-20). Overall survival and cause-specific survival were assessed with the Kaplan-Meier method at multiple timepoints (1 month, and year 1 to year 5) in our cohort. Multivariate Cox regression analysis was performed to identify prognostic factors.FINDINGSBased on NCC registries covering a population of 628·4 million, we estimated 43 275 new acute leukaemia cases and 27 049 deaths in 2019 in China, with an ASR for incidence 2·83 (95% CI 2·78-2·88) per 100 000 population and an ASR for mortality of 1·51 (1·48-1·54) per 100 000 population. The ASR for the incidence of non-acute promyelocytic leukaemia-acute myeloid leukaemia was 1·24 (95% CI 1·21-1·26) per 100 000 population, that of acute lymphoblastic leukaemia was 0·92 (0·89-0·95) per 100 000 population, and that of acute promyelocytic leukaemia was 0·22 (0·21-0·23) per 100 000 population. The incidence of acute leukaemia spiked in children aged 1-4 years (4·54 per 100 000), then declined, and then rose markedly after age 60 years, peaking at 9·33 per 100 000 in people aged 75-79 years, before declining, while overall mortality remained relatively low across younger age groups (0-44 years), then increased progressively with advancing age, from 1·23 per 100 000 in adults aged 45-49 years to 8·77 per 100 000 in those aged 80-84 years. In children, 5-year overall survival was 66·5% (95% CI 65·3-67·9) for non-acute promyelocytic leukaemia acute myeloid leukaemia, 91·1% (89·6-92·6) for acute promyelocytic leukaemia, and 85·4% (84·9-85·8) for acute lymphoblastic leukaemia; in adults, 5-year overall survival was 23·9% (23·4-24·3) for non-acute promye","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"34 1","pages":"e808-e822"},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishing a sustainable academic point-of-care network for CAR T-cell therapy.","authors":"Eulàlia Olesti,Mireia Bachiller,Aina Oliver-Caldés,Álvaro Urbano-Ispizua, ","doi":"10.1016/s2352-3026(25)00258-3","DOIUrl":"https://doi.org/10.1016/s2352-3026(25)00258-3","url":null,"abstract":"","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"9 1","pages":"e774-e776"},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sickle cell disease: a neglected health priority.","authors":" The Lancet Haematology","doi":"10.1016/s2352-3026(25)00260-1","DOIUrl":"https://doi.org/10.1016/s2352-3026(25)00260-1","url":null,"abstract":"","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"87 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indicators of inequity in research and funding for sickle cell disease, cystic fibrosis and haemophilia: a descriptive comparative study.","authors":"Rutendo Muzambi,Alex Bottle,Daniel Dexter,Cherelle Augustine,Jeannine Joseph,Funmi Dasaolu,Siobhán B Carr,Carl Reynolds,Ganesh Sathyamoorthy,John James,Frédéric B Piel","doi":"10.1016/s2352-3026(25)00235-2","DOIUrl":"https://doi.org/10.1016/s2352-3026(25)00235-2","url":null,"abstract":"BACKGROUNDSickle cell disease, one of the most common genetic conditions in the UK, is often considered a neglected disorder, but rigorous quantitative evidence to support this view is scarce. Comparative research of multiple conditions offers an effective way to document inequity and to guide public health policies. Therefore, we aimed to compare indicators of inequity in research and funding for sickle cell disease, cystic fibrosis, and haemophilia in the UK.METHODSIn this descriptive comparative study, we compiled publicly available data on disease prevalence for sickle cell disease, cystic fibrosis, and haemophilia, alongside seven comparative indicators: the number and value of grants from UK public health research funders (the Wellcome Trust, the National Institute for Health and Care Research, and UK Research and Innovation); resources available to dedicated charities (the Sickle Cell Society, the Cystic Fibrosis Trust, and the Haemophilia Society); characteristics of disease registries (the National Haemoglobinopathy Register, the UK Cystic Fibrosis Registry, and the UK National Haemophilia Database); the number of registered clinical trials (the National Library of Medicine Clinical Trials and the EU clinical trials register); number of scientific publications (PubMed); number of drug approvals (the Medicines and Healthcare products Regulatory Agency); and online disease awareness (Google Trends and Glimpse). We conducted descriptive analyses, including counts, proportions, means, and ratios.FINDINGSWe found marked differences in the seven indicators considered. Sickle cell disease was usually the most neglected condition, particularly when accounting for the number of people affected. The mean annual research funding per person was almost four times higher for cystic fibrosis (£704 [95% CI 697-710]) than for sickle cell disease (£184 [172-196]), and two times higher than for haemophilia (£315 [226-404]). There was one clinical trial per 273 people with sickle cell disease, compared with one trial per 53 and 55 people for cystic fibrosis and haemophilia, respectively. The mean annual number of publications was almost twice higher for cystic fibrosis (2431) than for sickle cell disease (1359) or haemophilia (1193).INTERPRETATIONThe comparative evidence provided support the view that sickle cell disease is neglected compared with cystic fibrosis and haemophilia in relation to research and funding in the UK. The highest value for each indicator, often observed for cystic fibrosis, provides a benchmark target for the other two conditions. More dedicated research funding would likely have a ripple effect on other indicators, which could guide public health policies and have a major effect on the quality of life of people living with sickle cell disease.FUNDINGNHS Race and Health Observatory.","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rituximab, bendamustine, and cytarabine followed by venetoclax in older patients with high-risk mantle cell lymphoma (FIL_V-RBAC): a multicentre, single-arm, phase 2 study.","authors":"Carlo Visco,Valentina Tabanelli,Maria Vittoria Sacchi,Andrea Evangelista,Francesca Maria Quaglia,Stefano Fiori,Riccardo Bomben,Maria Chiara Tisi,Marcello Riva,Anna Merli,Francesco Rotondo,Costanza Fraenza,Maria Elena Carazzolo,Paolo Corradini,Lucia Farina,Claudia Castellino,Alessia Castellino,Vittorio Ruggero Zilioli,Cristina Muzi,Francesco Piazza,Alessandro Re,Stefan Hohaus,Francesca Gaia Rossi,Gerardo Musuraca,Alice Di Rocco,Benedetta Puccini,Roberta Sciarra,Filippo Ballerini,Federica Cavallo,Riccardo Bruna,Riccardo Moia,Alessia Moioli,Andrea Bernardelli,Daniela Drandi,Annalisa Arcari,Francesco Merli,Guido Gini,Roberto Freilone,Monica Tani,Vincenzo Pavone,Marco Ladetto,Stefano Aldo Pileri,Monica Balzarotti, ","doi":"10.1016/s2352-3026(25)00252-2","DOIUrl":"https://doi.org/10.1016/s2352-3026(25)00252-2","url":null,"abstract":"BACKGROUNDBendamustine and rituximab combined with intermediate-dose cytarabine (RBAC) is one of the standard initial treatments for older, fit patients with mantle cell lymphoma. We aimed to investigate whether the addition of venetoclax to RBAC would improve progression-free survival in patients with high-risk mantle cell lymphoma.METHODSFIL_V-RBAC was a multicentre, single-arm, phase 2 study done in 35 institutions of the Fondazione Italiana Linfomi in Italy. Treatment-naive patients with a histological diagnosis of mantle cell lymphoma, aged 65 years or older and fit according to the Fondazione Italiana Linfomi modified comprehensive geriatric assessment (or younger than 65 years and ineligible for high-dose chemotherapy with Eastern Cooperative Oncology Group performance status of 2 or less), were classified after enrolment as having low-risk or high-risk disease, based on the presence of blastoid morphology, Ki67 30% or higher, TP53, or 17p deletion. Patients with a low-risk profile received RBAC intravenously (rituximab 375 mg/m2 and day 1; bendamustine 70 mg/m2 on days 1 and 2; and cytarabine 500 mg/m2 on days 1, 2, and 3) every 4 weeks for 6 cycles. Patients with a high-risk profile received four cycles of RBAC followed by fixed-duration oral venetoclax consolidation (4 months, 800 mg/day) and maintenance (20 months, 400 mg/day). The primary endpoint was 2-year progression-free survival for patients with a high-risk profile who received at least one dose of RBAC. This trial was registered with ClinicalTrials.gov, NCT03567876, and this is the final report.FINDINGSBetween Sept 10, 2018, and July 26, 2021, 155 patients were screened for inclusion, 140 of whom were enrolled and analysed for study endpoints. Median age was 72 (IQR 69-76), 107 (76%) patients were male, 33 (24%) were female, and all were White. 54 (39%) patients had a high-risk profile (28 [20%] with TP53 mutations, 19 [14%] with 17p deletions, 34 [24%] with Ki67 ≥30%, and 13 [9%] with a blastoid morphology) and 86 (61%) had a low-risk profile. After a median follow-up of 45 months (IQR 40-55), the 2-year progression-free survival in the high-risk group was 60% (95% CI 48-74) and the median progression-free survival was 37 months (95% CI 19-not reached). The most frequent grade 3 or worse adverse events during venetoclax consolidation were neutropenia (12 [28%] of 43 patients), followed by thrombocytopenia (three [7%]) and skin reactions (three [7%]). During venetoclax maintenance, the most frequent grade 3 or worse adverse events were neutropenia (seven [19%] of 37 patients), followed by thrombocytopenia (two [5%]) and anaemia (two [5%]). One (1%) of 140 patients had a treatment-related death (tumour lysis syndrome during first induction with RBAC in a patient with a high-risk profile).INTERPRETATIONTo our knowledge, this is the first prospective study to stratify patients with mantle cell lymphoma to different treatments according to their risk profile. Our results suggest th","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}