The Lancet Haematology最新文献

{"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":"2 1","pages":""},"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}

{"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":"37 1","pages":""},"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}

{"title":"Improving equity for people living with rare diseases","authors":"","doi":"10.1016/s2352-3026(24)00011-5","DOIUrl":"https://doi.org/10.1016/s2352-3026(24)00011-5","url":null,"abstract":"Abstract not available","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139577753","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":"Prospective characterisation of non-malignant, paediatric lymphoproliferative disease","authors":"Troy R Torgerson","doi":"10.1016/s2352-3026(24)00002-4","DOIUrl":"https://doi.org/10.1016/s2352-3026(24)00002-4","url":null,"abstract":"Abstract not available","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139577789","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":"A treatise on clinical trials","authors":"Talal Hilal","doi":"10.1016/s2352-3026(24)00009-7","DOIUrl":"https://doi.org/10.1016/s2352-3026(24)00009-7","url":null,"abstract":"Abstract not available","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"165 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139577782","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":"Lallindra Gooneratne—maintaining treatment flow amid crisis","authors":"Ray Cavanaugh","doi":"10.1016/s2352-3026(24)00008-5","DOIUrl":"https://doi.org/10.1016/s2352-3026(24)00008-5","url":null,"abstract":"Abstract not available","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139660369","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":"Acute promyelocytic leukaemia in low-income and middle-income countries: a Brazilian experience","authors":"Diego A Pereira-Martins, Isabel Weinhäuser, Juan L Coelho-Silva, Emanuele Ammatuna, Gerwin Huls, Jan Jacob Schuringa, Eduardo M Rego, Antonio R Lucena-Araujo","doi":"10.1016/s2352-3026(23)00396-4","DOIUrl":"https://doi.org/10.1016/s2352-3026(23)00396-4","url":null,"abstract":"Abstract not available","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139577582","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":"Elotuzumab, lenalidomide, bortezomib, dexamethasone, and autologous haematopoietic stem-cell transplantation for newly diagnosed multiple myeloma (GMMG-HD6): results from a randomised, phase 3 trial","authors":"Elias K Mai, Hartmut Goldschmid, Kaya Miah, Uta Bertsch, Britta Besemer, Mathias Hänel, Julia Krzykalla, Roland Fenk, Jana Schlenzka, Markus Munder, Jan Dürig, Igor W Blau, Stefanie Huhn, Dirk Hose, Anna Jauch, Christina Kunz, Christoph Mann, Niels Weinhold, Christof Scheid, Roland Schroers, Iris Zirpel","doi":"10.1016/s2352-3026(23)00366-6","DOIUrl":"https://doi.org/10.1016/s2352-3026(23)00366-6","url":null,"abstract":"<h3>Background</h3><p>The aim of this trial was to investigate the addition of the anti-SLAMF7 monoclonal antibody elotuzumab to lenalidomide, bortezomib, and dexamethasone (RVd) in induction and consolidation therapy as well as to lenalidomide maintenance treatment in transplant-eligible patients with newly diagnosed multiple myeloma.</p><h3>Methods</h3><p>GMMG-HD6 was a phase 3, randomised trial conducted at 43 main trial sites and 26 associated trial sites throughout Germany. Adult patients (aged 18–70 years) with previously untreated, symptomatic multiple myeloma, and a WHO performance status of 0–3, with 3 being allowed only if caused by myeloma disease and not by comorbid conditions, were randomly assigned 1:1:1:1 to four treatment groups. Induction therapy consisted of four 21-day cycles of RVd (lenalidomide 25 mg orally on days 1–14; bortezomib 1·3 mg/m² subcutaneously on days 1, 4, 8, and 11]; and dexamethasone 20 mg orally on days 1, 2, 4, 5, 8, 9, 11, 12, and 15 for cycles 1–2) or, RVd induction plus elotuzumab (10 mg/kg intravenously on days 1, 8, and 15 for cycles 1–2, and on days 1 and 11 for cycles 3–4; E-RVd). Autologous haematopoietic stem-cell transplantation was followed by two 21-day cycles of either RVd consolidation (lenalidomide 25 mg orally on days 1–14; bortezomib 1·3 mg/m² subcutaneously on days 1, 8, and 15; and dexamethasone 20 mg orally on days 1, 2, 8, 9, 15, and 16) or elotuzumab plus RVd consolidation (with elotuzumab 10 mg/kg intravenously on days 1, 8, and 15) followed by maintenance with either lenalidomide (10 mg orally on days 1–28 for cycles 1–3; thereafter, up to 15 mg orally on days 1–28; RVd/R or E-RVd/R group) or lenalidomide plus elotuzumab (10 mg/kg intravenously on days 1 and 15 for cycles 1–6, and on day 1 for cycles 7–26; RVd/E-R or E-RVd/E-R group) for 2 years. The primary endpoint was progression-free survival analysed in a modified intention-to-treat (ITT) population. Safety was analysed in all patients who received at least one dose of trial medication. This trial is registered with <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>NCT02495922</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 completed.</p><h3>Findings</h3><p>Between June 29, 2015, and on Sept 11, 2017, 564 patients were included in the trial. The modified ITT population comprised 559 (243 [43%] females and 316 [57%] males) patients and the safety population 555 patients. After a median follow-up of 49·8 months (IQR 43·7–55·5), there was no difference in progression-free survival between the four treatment groups (adjusted log-rank p value","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139577686","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":"Advancements in haemophilia A and health equity: is it time to redefine severity?","authors":"Angela C Weyand, Lynn Malec, Steven W Pipe","doi":"10.1016/s2352-3026(23)00270-3","DOIUrl":"https://doi.org/10.1016/s2352-3026(23)00270-3","url":null,"abstract":"Abstract not available","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"105 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139577759","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":"Vacuoles in bone marrow progenitors: VEXAS syndrome and beyond","authors":"Valentin Lacombe, Jérome Hadjadj, Sophie Georgin-Lavialle, Christian Lavigne, Franck Geneviève, Olivier Kosmider","doi":"10.1016/s2352-3026(23)00375-7","DOIUrl":"https://doi.org/10.1016/s2352-3026(23)00375-7","url":null,"abstract":"<p><span>The presence of vacuoles in myeloid and erythroid progenitor cells in bone marrow aspirates is a key feature of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. The mere observation of vacuolated progenitor cells is not specific to VEXAS syndrome; in this Viewpoint, we point out the causes to be considered in this situation. Vacuoles, in particular, can be observed in individuals with wild-type </span><em>UBA1</em><span> and with persistent inflammatory features or myelodysplastic syndromes. However, several clues support the diagnosis of VEXAS syndrome in the presence of vacuolated bone marrow progenitors: a high number of vacuolated progenitors and of vacuoles per cell, the predominance of vacuoles in early rather than late progenitors, and the vacuolisation of both myeloid and erythroid progenitors with predominance of myeloid ones. Some criteria derived from these observations have been proposed with great diagnostic performances. However, the absence or a low proportion of vacuolated cells should not prevent </span><em>UBA1</em> gene sequencing.</p>","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139577766","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}