The Lancet Haematology最新文献

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Triplet therapy for advanced BCR::ABL1 positive myeloid leukaemias. 晚期BCR::ABL1阳性髓性白血病的三联疗法。
The Lancet Haematology Pub Date : 2024-09-17 DOI: 10.1016/s2352-3026(24)00282-5
Mhairi Copland
{"title":"Triplet therapy for advanced BCR::ABL1 positive myeloid leukaemias.","authors":"Mhairi Copland","doi":"10.1016/s2352-3026(24)00282-5","DOIUrl":"https://doi.org/10.1016/s2352-3026(24)00282-5","url":null,"abstract":"","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275330","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}
引用次数: 0
Decitabine, venetoclax, and ponatinib for advanced phase chronic myeloid leukaemia and Philadelphia chromosome-positive acute myeloid leukaemia: a single-arm, single-centre phase 2 trial. 地西他滨、venetoclax和泊纳替尼治疗晚期慢性髓性白血病和费城染色体阳性急性髓性白血病:单臂、单中心2期试验。
The Lancet Haematology Pub Date : 2024-09-17 DOI: 10.1016/s2352-3026(24)00250-3
Nicholas J Short,Daniel Nguyen,Elias Jabbour,Jayastu Senapati,Zhihong Zeng,Ghayas C Issa,Hussein Abbas,Cedric Nasnas,Wei Qiao,Xuelin Huang,Gautam Borthakur,Kelly Chien,Fadi G Haddad,Naveen Pemmaraju,Omer S Karrar,Danielle Nguyen,Marina Konopleva,Hagop Kantarjian,Farhad Ravandi
{"title":"Decitabine, venetoclax, and ponatinib for advanced phase chronic myeloid leukaemia and Philadelphia chromosome-positive acute myeloid leukaemia: a single-arm, single-centre phase 2 trial.","authors":"Nicholas J Short,Daniel Nguyen,Elias Jabbour,Jayastu Senapati,Zhihong Zeng,Ghayas C Issa,Hussein Abbas,Cedric Nasnas,Wei Qiao,Xuelin Huang,Gautam Borthakur,Kelly Chien,Fadi G Haddad,Naveen Pemmaraju,Omer S Karrar,Danielle Nguyen,Marina Konopleva,Hagop Kantarjian,Farhad Ravandi","doi":"10.1016/s2352-3026(24)00250-3","DOIUrl":"https://doi.org/10.1016/s2352-3026(24)00250-3","url":null,"abstract":"BACKGROUNDAdvanced phase Philadelphia chromosome-positive myeloid disease-consisting of chronic myeloid leukaemia in the myeloid blast phase and in the accelerated phase, and Philadelphia chromosome-positive acute myeloid leukaemia-is associated with poor outcomes. Although previous studies have suggested the benefit of chemotherapy and BCR::ABL1 tyrosine kinase inhibitor combinations, the optimal regimen is uncertain and prospective studies for this rare group of diseases are scant. Preclinical and retrospective clinical data suggest possible synergy between the BCL-2 inhibitor venetoclax and BCR::ABL1 tyrosine kinase inhibitors. We therefore aimed to design a study to evaluate the safety and activity of a novel combination of decitabine, venetoclax, and the third-generation BCR::ABL1 tyrosine kinase inhibitor ponatinib in advanced phase Philadelphia chromosome-positive myeloid diseases.METHODSFor this phase 2 study, patients aged 18 years or older with previously untreated or relapsed or refractory myeloid chronic myeloid leukaemia-blast phase, chronic myeloid leukaemia-accelerated phase, or advanced phase Philadelphia chromosome-positive acute myeloid leukaemia, and an Eastern Cooperative Oncology Group performance status of 0-3 were eligible. Patients were eligible regardless of the number of previous lines of therapy received or previous receipt of ponatinib. Cycle 1 (induction) consisted of a 7-day lead-in of ponatinib 45 mg orally daily (days 1-7), followed by combination therapy with decitabine 20 mg/m2 intravenously on days 8-12, venetoclax orally daily with ramp-up to a maximum dose of 400 mg on days 8-28, and ponatinib 45 mg orally daily on days 8-28. Cycles 2-24 consisted of decitabine 20 mg/m2 intravenously on days 1-5, venetoclax orally 400 mg on days 1-21, and ponatinib orally daily on days 1-28. Response-based dosing of ponatinib was implemented in consolidation cycles, with reduction to 30 mg daily in patients who reached complete remission or complete remission with an incomplete haematological recovery and a reduction to 15 mg daily in patients with undetectable BCR::ABL1 transcripts. The primary endpoint was the composite rate of complete remission or complete remission with incomplete haematological recovery in the intention-to-treat population. Safety was assessed in the intention-to-treat population. This trial was registered with ClinicalTrials.gov (NCT04188405) and is still ongoing.RESULTSBetween July 12, 2020, and July 8, 2023, 20 patients were treated (14 with chronic myeloid leukaemia-blast phase, four with chronic myeloid leukaemia-accelerated phase, and two with advanced phase Philadelphia chromosome-positive acute myeloid leukaemia). The median age was 43 years (IQR 32-58); 13 (65%) patients were male and seven (35%) were female; and 12 (60%) were White, three (15%) were Hispanic, four (20%) were Black, and one (5%) was Asian. 12 (60%) patients had received 2 or more previous BCR::ABL1 tyrosine kinase inhibitors, an","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275331","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}
引用次数: 0
Efficacy and safety of fedratinib in patients with myelofibrosis previously treated with ruxolitinib (FREEDOM2): results from a multicentre, open-label, randomised, controlled, phase 3 trial. 既往接受过鲁索利替尼治疗的骨髓纤维化患者服用非瑞替尼的疗效和安全性(FREEDOM2):一项多中心、开放标签、随机对照、三期试验的结果。
The Lancet Haematology Pub Date : 2024-09-09 DOI: 10.1016/s2352-3026(24)00212-6
Claire N Harrison,Ruben Mesa,Moshe Talpaz,Haifa Kathrin Al-Ali,Blanca Xicoy,Francesco Passamonti,Francesca Palandri,Giulia Benevolo,Alessandro Maria Vannucchi,Clemence Mediavilla,Alessandra Iurlo,InHo Kim,Shelonitda Rose,Patrick Brown,Christopher Hernandez,Jia Wang,Jean-Jacques Kiladjian
{"title":"Efficacy and safety of fedratinib in patients with myelofibrosis previously treated with ruxolitinib (FREEDOM2): results from a multicentre, open-label, randomised, controlled, phase 3 trial.","authors":"Claire N Harrison,Ruben Mesa,Moshe Talpaz,Haifa Kathrin Al-Ali,Blanca Xicoy,Francesco Passamonti,Francesca Palandri,Giulia Benevolo,Alessandro Maria Vannucchi,Clemence Mediavilla,Alessandra Iurlo,InHo Kim,Shelonitda Rose,Patrick Brown,Christopher Hernandez,Jia Wang,Jean-Jacques Kiladjian","doi":"10.1016/s2352-3026(24)00212-6","DOIUrl":"https://doi.org/10.1016/s2352-3026(24)00212-6","url":null,"abstract":"BACKGROUNDMost patients with myelofibrosis develop ruxolitinib intolerance or disease that is relapsed or refractory, and survival rates after ruxolitinib discontinuation are poor. We aimed to evaluate the safety and efficacy of fedratinib versus best available therapy (BAT) in patients with myelofibrosis previously treated with ruxolitinib.METHODSFREEDOM2 was a multicentre, open-label, randomised, controlled, phase 3 trial in 86 clinics in 16 countries, in which patients aged at least 18 years with intermediate-2 or high-risk myelofibrosis that was relapsed or refractory or intolerant to ruxolitinib with Eastern Cooperative Oncology Group performance status 0-2 were stratified by spleen size by palpation, platelet count, and previous ruxolitinib treatment, and randomly assigned 2:1 by interactive response technology to receive fedratinib 400 mg per day (4 × 100 mg capsules orally once daily, open-label) or BAT. Patients received prophylactic antiemetics and thiamine supplementation, and symptomatic antidiarrhoeals as required. Primary endpoint was proportion of patients reaching spleen volume reduction (SVR) of at least 35% (SVR35) at end of cycle 6 in the intention-to-treat population. This manuscript reports the primary analysis of the trial; follow-up is ongoing. This trial is registered at clinicaltrials.gov, NCT03952039.FINDINGSBetween Sept 9, 2019 and June 24, 2022, of 316 patients screened, 201 were randomly assigned and treated (134 to fedratinib, 67 to BAT [including 52 receiving ruxolitinib]); 46 patients from the BAT group crossed over to fedratinib. Approximately half of enrolled patients were male (fedratinib 75 [56%] of 134; BAT 30 [45%] of 67) and most were White (fedratinib 106 [79%] of 134; BAT 58 [87%] of 67). At data cutoff (Dec 27, 2022), median survival follow-up was 64·5 weeks (IQR 37·9-104·9). SVR35 at end of cycle 6 was seen in 48 (36%) of 134 patients receiving fedratinib versus four (6%) of 67 patients receiving BAT (30% difference; 95% CI 20-39; one-sided p-value <0·0001). During the first six cycles 53 (40%) of 134 patients in the fedratinib group and 8 (12%) of 67 patients in the BAT group had grade 3 or greater treatment-related adverse events, most frequently anaemia (fedratinib 12 [9%] of 134; BAT 6 [9%] of 67) and thrombocytopenia (fedratinib 16 [12%] of 134; BAT 2 [3%] of 67); one patient in the fedratinib group died from acute kidney injury suspected to be related to study drug (no treatment-related deaths in the BAT group). Gastrointestinal adverse events occurred more frequently in the fedratinib group compared with the BAT group, but were mostly grade 1-2 in severity and more frequent in early cycles, and were less frequent than in prior clinical trials. A total of 28 (21%) of 134 patients in the fedratinib group and 3 (4%) of 67 patients in the BAT group had thiamine levels below lower limit of normal per central laboratory assessment, with only one case of low thiamine in the fedratinib arm after the intro","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231512","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}
引用次数: 0
Ixazomib as consolidation and maintenance versus observation in patients with relapsed multiple myeloma eligible for salvage autologous stem-cell transplantation (Myeloma XII [ACCoRD]): interim analysis of a multicentre, open-label, randomised, phase 3 trial. 伊沙佐米对符合自体干细胞移植挽救条件的复发性多发性骨髓瘤患者的巩固和维持治疗与观察治疗(骨髓瘤 XII [ACCoRD]):一项多中心、开放标签、随机、3 期试验的中期分析。
The Lancet Haematology Pub Date : 2024-09-06 DOI: 10.1016/s2352-3026(24)00249-7
Gordon Cook,A John Ashcroft,Ethan Senior,Catherine Olivier,Anna Hockaday,Jeanine Richards,Jamie D Cavenagh,John A Snowden,Mark T Drayson,Ruth de Tute,Lesley Roberts,Roger G Owen,Kwee Yong,Mamta Garg,Kevin Boyd,Hamdi Sati,Sharon Gillson,Mark Cook,David A Cairns,Christopher Parrish,
{"title":"Ixazomib as consolidation and maintenance versus observation in patients with relapsed multiple myeloma eligible for salvage autologous stem-cell transplantation (Myeloma XII [ACCoRD]): interim analysis of a multicentre, open-label, randomised, phase 3 trial.","authors":"Gordon Cook,A John Ashcroft,Ethan Senior,Catherine Olivier,Anna Hockaday,Jeanine Richards,Jamie D Cavenagh,John A Snowden,Mark T Drayson,Ruth de Tute,Lesley Roberts,Roger G Owen,Kwee Yong,Mamta Garg,Kevin Boyd,Hamdi Sati,Sharon Gillson,Mark Cook,David A Cairns,Christopher Parrish,","doi":"10.1016/s2352-3026(24)00249-7","DOIUrl":"https://doi.org/10.1016/s2352-3026(24)00249-7","url":null,"abstract":"BACKGROUNDThe efficacy of consolidation and maintenance in the context of salvage autologous haematopoietic stem-cell transplantation (HSCT) for relapsed multiple myeloma remains unclear. We aimed to assess whether consolidation after salvage autologous HSCT, using ixazomib, thalidomide, and dexamethasone, followed by maintenance with single agent ixazomib is superior to observation.METHODSThis is an interim analysis of Myeloma XII (ACCorD; referred to as ACCorD hereafter), an open-label, randomised, controlled, phase 3 trial done at 79 hospitals in the UK. Eligible patients were aged 18 years or older, had relapsed multiple myeloma with measurable disease, an ECOG performance status of 2 or less with adequate renal, hepatobiliary, pulmonary, and cardiac function, and required treatment for first progressive disease occurring at least 12 months after first autologous HSCT. In a first randomisation, patients were assigned (1:1) to receive either conventional autologous HSCT with melphalan or augmented autologous HSCT with melphalan and ixazomib. In the second randomisation, reported here, patients were assigned (1:1) to consolidation using ixazomib, thalidomide, and dexamethasone (oral ixazomib 4 mg per day on days 1, 8, and 15, oral thalidomide 100 mg per day on days 1-28, and oral dexamethasone 40 mg per day on days 1, 8, 15 and 22 of 28-day cycles), followed by maintenance with single agent ixazomib (oral ixazomib 4 mg per day on days 1, 8, and 15 of 28-day cycles until disease progression or intolerance), or observation. The primary endpoint was progression-free survival, analysed by intention-to-treat. Safety was analysed per-protocol. This study is registered with ISRCTN, ISRCTN10038996, and EudraCT, 2016-000905-35, and recruitment is complete.FINDINGSBetween Dec 12, 2017, and April 21, 2023, 206 patients entered the second randomisation (103 in the consolidation and maintenance group and 103 in the observation group). This prespecified interim analysis (data cutoff April 21, 2023), was done at a median follow-up of 27 months (IQR 13-38). Median progression-free survival was 20 months (95% CI 15-29) in the consolidation and maintenance group and 13 months (11-18) in the observation group (hazard ratio 0·55 [95% CI 0·39-0·78]; p=0·0006). Serious adverse events were reported in 29 (32%) of 92 patients in the consolidation and maintenance group compared with seven (7%) of 103 patients in the observation group. The most common serious adverse events were infections and infestations in both the consolidation and maintenance group and the observation group. The most common grade 3, 4, or 5 adverse events for patients in the consolidation and maintenance group were upper respiratory infection (seven [8%] of 92 patients). No deaths in the consolidation and maintenance group were deemed treatment related.INTERPRETATIONACCorD provides evidence that an orally administered, deliverable, and tolerable post-salvage autologous HSCT treatment regimen can im","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142165848","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}
引用次数: 0
Continued need for autologous transplantation in relapsed myeloma. 复发骨髓瘤患者仍需进行自体移植。
The Lancet Haematology Pub Date : 2024-09-06 DOI: 10.1016/s2352-3026(24)00277-1
Elias K Mai
{"title":"Continued need for autologous transplantation in relapsed myeloma.","authors":"Elias K Mai","doi":"10.1016/s2352-3026(24)00277-1","DOIUrl":"https://doi.org/10.1016/s2352-3026(24)00277-1","url":null,"abstract":"","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142165904","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}
引用次数: 0
Pembrolizumab and low-dose, single-fraction radiotherapy for patients with relapsed or refractory multiple myeloma: a prospective, single-centre, single-group, open-label, phase 2 pilot trial in the USA 针对复发或难治性多发性骨髓瘤患者的 Pembrolizumab 和低剂量单剂量放疗:在美国进行的一项前瞻性、单中心、单组、开放标签的 2 期试点试验
The Lancet Haematology Pub Date : 2024-05-01 DOI: 10.1016/s2352-3026(24)00105-4
Mohammad K Khan, T. Nasti, Joshua Y Qian, T. Kleber, Jeffrey M Switchenko, J. Kaufman, Ajay J Nooka, M. Dhodapkar, Z. Buchwald, Daby Obiekwe, S. Lonial, Rafi Ahmed
{"title":"Pembrolizumab and low-dose, single-fraction radiotherapy for patients with relapsed or refractory multiple myeloma: a prospective, single-centre, single-group, open-label, phase 2 pilot trial in the USA","authors":"Mohammad K Khan, T. Nasti, Joshua Y Qian, T. Kleber, Jeffrey M Switchenko, J. Kaufman, Ajay J Nooka, M. Dhodapkar, Z. Buchwald, Daby Obiekwe, S. Lonial, Rafi Ahmed","doi":"10.1016/s2352-3026(24)00105-4","DOIUrl":"https://doi.org/10.1016/s2352-3026(24)00105-4","url":null,"abstract":"","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141141311","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}
引用次数: 0
Diagnosis and management of pyruvate kinase deficiency: international expert guidelines 丙酮酸激酶缺乏症的诊断和管理:国际专家指南
The Lancet Haematology Pub Date : 2024-02-05 DOI: 10.1016/s2352-3026(23)00377-0
Hanny Al-Samkari, Nadine Shehata, Kelly Lang-Robertson, Paola Bianchi, Andreas Glenthøj, Sujit Sheth, Ellis J Neufeld, David C Rees, Satheesh Chonat, Kevin H M Kuo, Jennifer A Rothman, Wilma Barcellini, Eduard J van Beers, Dagmar Pospíšilová, Ami J Shah, Richard van Wijk, Bertil Glader, Maria Del Mar Mañú Pereira, Oliver Andres, Theodosia A Kalfa, Rachael F Grace
{"title":"Diagnosis and management of pyruvate kinase deficiency: international expert guidelines","authors":"Hanny Al-Samkari, Nadine Shehata, Kelly Lang-Robertson, Paola Bianchi, Andreas Glenthøj, Sujit Sheth, Ellis J Neufeld, David C Rees, Satheesh Chonat, Kevin H M Kuo, Jennifer A Rothman, Wilma Barcellini, Eduard J van Beers, Dagmar Pospíšilová, Ami J Shah, Richard van Wijk, Bertil Glader, Maria Del Mar Mañú Pereira, Oliver Andres, Theodosia A Kalfa, Rachael F Grace","doi":"10.1016/s2352-3026(23)00377-0","DOIUrl":"https://doi.org/10.1016/s2352-3026(23)00377-0","url":null,"abstract":"<p><span>Pyruvate kinase (PK) deficiency is the most common cause of chronic congenital non-spherocytic haemolytic anaemia worldwide, with an estimated prevalence of one in 100 000 to one in 300 000 people. PK deficiency results in chronic haemolytic anaemia, with wide ranging and serious consequences affecting health, </span>quality of life<span>, and mortality. The goal of the International Guidelines for the Diagnosis and Management of Pyruvate Kinase Deficiency was to develop evidence-based guidelines for the clinical care of patients with PK deficiency. These clinical guidelines were developed by use of GRADE methodology and the AGREE II framework. Experts were invited after consideration of area of expertise, scholarly contributions in PK deficiency, and country of practice for global representation. The expert panel included 29 expert physicians (including adult and paediatric haematologists and other subspecialists), geneticists, laboratory specialists, nurses, a guidelines methodologist, patients with PK deficiency, and caregivers from ten countries. Five key topic areas were identified, the panel prioritised key questions, and a systematic literature search was done to generate evidence summaries that were used in the development of draft recommendations. The expert panel then met in person to finalise and vote on recommendations according to a structured consensus procedure. Agreement of greater than or equal to 67% among the expert panel was required for inclusion of a recommendation in the final guideline. The expert panel agreed on 31 total recommendations across five key topics: diagnosis and genetics, monitoring and management of chronic complications, standard management of anaemia, targeted and advanced therapies, and special populations. These new guidelines should facilitate best practices and evidence-based PK deficiency care into clinical practice.</span></p>","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139695694","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}
引用次数: 0
Correction to Lancet Haematol 2024; 11: e38–50 Lancet Haematol 2024; 11: e38-50 更正
The Lancet Haematology Pub Date : 2024-02-05 DOI: 10.1016/s2352-3026(24)00035-8
{"title":"Correction to Lancet Haematol 2024; 11: e38–50","authors":"","doi":"10.1016/s2352-3026(24)00035-8","DOIUrl":"https://doi.org/10.1016/s2352-3026(24)00035-8","url":null,"abstract":"Abstract not available","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139695576","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}
引用次数: 0
Oral decitabine plus cedazuridine and venetoclax in patients with higher-risk myelodysplastic syndromes or chronic myelomonocytic leukaemia: a single-centre, phase 1/2 study 在高风险骨髓增生异常综合征或慢性粒细胞白血病患者中口服地西他滨加西达嘧啶和 Venetoclax:一项单中心、1/2 期研究
The Lancet Haematology Pub Date : 2024-02-02 DOI: 10.1016/s2352-3026(23)00367-8
Alex Bataller, Guillermo Montalban-Bravo, Alexandre Bazinet, Yesid Alvarado, Kelly Chien, Sangeetha Venugopal, Jo Ishizawa, Danielle Hammond, Mahesh Swaminathan, Koji Sasaki, Ghayas C Issa, Nicholas J Short, Lucia Masarova, Naval G Daver, Tapan M Kadia, Simona Colla, Wei Qiao, Xuelin Huang, Rashmi Kanagal-Shamanna, Stephany Hendrickson, Guillermo Garcia-Manero
{"title":"Oral decitabine plus cedazuridine and venetoclax in patients with higher-risk myelodysplastic syndromes or chronic myelomonocytic leukaemia: a single-centre, phase 1/2 study","authors":"Alex Bataller, Guillermo Montalban-Bravo, Alexandre Bazinet, Yesid Alvarado, Kelly Chien, Sangeetha Venugopal, Jo Ishizawa, Danielle Hammond, Mahesh Swaminathan, Koji Sasaki, Ghayas C Issa, Nicholas J Short, Lucia Masarova, Naval G Daver, Tapan M Kadia, Simona Colla, Wei Qiao, Xuelin Huang, Rashmi Kanagal-Shamanna, Stephany Hendrickson, Guillermo Garcia-Manero","doi":"10.1016/s2352-3026(23)00367-8","DOIUrl":"https://doi.org/10.1016/s2352-3026(23)00367-8","url":null,"abstract":"<h3>Background</h3><p><span>Hypomethylating agents are approved in higher-riskmyelodysplastic syndromes. The combination of a hypomethylating agent with </span>venetoclax<span><span> is standard of care in acute myeloid leukaemia. We investigated the safety and activity of the first totally oral combination of </span>decitabine<span><span> plus cedazuridine and venetoclax </span>in patients with higher-risk-myelodysplastic syndromes and chronic myelomonocytic leukaemia.</span></span></p><h3>Methods</h3><p><span>We did a single-centre, dose-escalation and dose-expansion, phase 1/2, clinical trial. Patients with treatment-naive higher-risk-myelodysplastic syndromes or chronic myelomonocytic leukaemia (risk level categorised as intermediate-2 or higher by the International Prognostic Scoring System) with excess blasts (&gt;5%). Treatment consisted of oral decitabine 35 mg plus cedazuridine 100 mg on days 1–5 and venetoclax (variable doses of 100–400 mg, day 1 to 14, 28-day cycle). The primary outcomes were safety for the phase 1 part and the overall response for the phase 2 part of the study. The trial is ongoing and this analysis was not prespecified. This study is registered with </span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"8px\" viewbox=\"0 0 8 8\" width=\"8px\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg>, <span>NCT04655755</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"8px\" viewbox=\"0 0 8 8\" width=\"8px\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg>, and is currently enrolling participants.</p><h3>Findings</h3><p><span>Between Jan 21, 2021, and Jan 20, 2023, we enrolled 39 patients (nine in phase 1 and 30 in phase 2). The median age was 71 years (range 27–94), 28 (72%) patients were male, and 11 (28%) were female. The maximum tolerated dose was not reached, and the recommended phase 2 dose was established as oral decitabine 35 mg plus cedazuridine 100 mg for 5 days and venetoclax (400 mg) for 14 days. The most common grade 3–4 adverse events were thrombocytopenia (33 [85%] of 39), neutropenia (29 [74%]), and febrile neutropenia (eight [21%]). Four non-treatment-related deaths occurred on the study </span>drugs due to sepsis (n=2), lung infection (n=1), and undetermined cause (n=1). The median follow-up time was 10·8 months (IQR 5·6–16·4). The overall response rate was 95% (95% CI 83-99; 37/39). 19 (49%) patients proceeded to hematopoietic stem-cell transplantation.</p><h3>Interpretation</h3><p>This early analysis suggests that the combination of oral decitabine plus cedazuridine with venetoclax for higher-risk-myelodysplastic syndromes and chronic myelomonocytic leukaemia is safe in most patients, with encouraging activity. Longer follow-up will be needed to confirm these data.</p><h3>Funding</h3><p>MD Anderson Cancer Center, MDS/AML Moon ","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139660421","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}
引用次数: 0
Decitabine plus cedazuridine and venetoclax: the promise of an all-oral therapy for patients with myelodysplastic syndromes and chronic myelomonocytic leukaemia 地西他滨加西达嘧啶和 Venetoclax:骨髓增生异常综合征和慢性粒细胞白血病患者的全口服疗法前景看好
The Lancet Haematology Pub Date : 2024-02-02 DOI: 10.1016/s2352-3026(24)00001-2
Sarit Assouline
{"title":"Decitabine plus cedazuridine and venetoclax: the promise of an all-oral therapy for patients with myelodysplastic syndromes and chronic myelomonocytic leukaemia","authors":"Sarit Assouline","doi":"10.1016/s2352-3026(24)00001-2","DOIUrl":"https://doi.org/10.1016/s2352-3026(24)00001-2","url":null,"abstract":"Abstract not available","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139660366","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}
引用次数: 0
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