Lancet Haematology最新文献

{"title":"Optimising quadruplet regimens to broaden eligibility in multiple myeloma.","authors":"Tanya M Wildes","doi":"10.1016/S2352-3026(24)00356-9","DOIUrl":"https://doi.org/10.1016/S2352-3026(24)00356-9","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"12 2","pages":"e87-e88"},"PeriodicalIF":15.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256969","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}

{"title":"Patient reported outcomes with earlier use of chimeric antigen receptor-T cell therapy in multiple myeloma.","authors":"Alissa Visram, Hira Mian","doi":"10.1016/S2352-3026(24)00346-6","DOIUrl":"https://doi.org/10.1016/S2352-3026(24)00346-6","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"12 1","pages":"e6-e8"},"PeriodicalIF":15.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933197","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}

{"title":"Oreofe Odejide-aiming to raise the bar in haematology care.","authors":"Tony Kirby","doi":"10.1016/S2352-3026(24)00380-6","DOIUrl":"https://doi.org/10.1016/S2352-3026(24)00380-6","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"12 1","pages":"e10"},"PeriodicalIF":15.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933196","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}

{"title":"Accelerating and optimising CAR T-cell manufacture to deliver better patient products.","authors":"Giulia Agliardi, Juliana Dias, Alexandros Rampotas, John Garcia, Claire Roddie","doi":"10.1016/S2352-3026(24)00273-4","DOIUrl":"10.1016/S2352-3026(24)00273-4","url":null,"abstract":"<p><p>Autologous chimeric antigen receptor (CAR) T-cell therapy has transformed the management of B-cell leukaemia and lymphoma. However, current manufacturing processes present logistical hurdles, restricting broader application. As clinical outcomes can be heavily influenced by the quality of autologous starting materials and production processes, strategies to improve product phenotype are crucial. Short manufacturing processes have the advantage of bringing products to patients more quickly and, in parallel, avoiding the highly differentiated and exhausted CAR T-cell phenotypes associated with prolonged ex vivo manufacture. This Review examines advances in our understanding of what constitutes an effective CAR T-cell product and approaches to improve product quality. Historically, strategies have relied on adjustments in medium composition and selection of less differentiated cell subtypes. Since 2020, the field has been shifting towards reduced-expansion protocols, no-activation protocols, and point-of-care manufacturing. These approaches have the advantage of a rapid turnaround while maintaining a less differentiated and exhausted phenotype. These efforts are leading to ultrarapid production methods and even elimination of ex vivo manipulation with the use of in vivo manufacturing approaches. In this Review, we focus on the advances needed to accelerate CAR T-cell manufacture (including near-patient methods), with an emphasis on improved therapeutic efficacy and rapid turnaround time, and simplified quality control procedures required to fully realise the clinical potential of CAR T-cell therapies.</p>","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e57-e67"},"PeriodicalIF":15.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607025","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}

{"title":"Safety and efficacy of mitapivat in sickle cell disease (RISE UP): results from the phase 2 portion of a global, double-blind, randomised, placebo-controlled trial.","authors":"Modupe Idowu, Lucas Otieno, Bogdan Dumitriu, Clarisse L C Lobo, Swee Lay Thein, Biree Andemariam, Obiageli E Nnodu, Adlette Inati, Alexander K Glaros, Pablo Bartolucci, Raffaella Colombatti, Ali T Taher, Miguel R Abboud, Deepika Darbari, Kenneth I Ataga, Ali Bülent Antmen, Kevin H M Kuo, Samuel de Souza Medina, Abdulafeez Oluyadi, Varsha Iyer, Susan Morris, Amber M Yates, Hui Shao, Spurthi Patil, Rolandas Urbstonaitis, Ahmar U Zaidi, Sarah Gheuens, Wally R Smith","doi":"10.1016/S2352-3026(24)00319-3","DOIUrl":"10.1016/S2352-3026(24)00319-3","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Sickle cell disease, a debilitating, inherited haemolytic anaemia with premature morbidity and mortality, affects millions globally. Mitapivat, a first-in-class, oral, allosteric activator of pyruvate kinase, improves red blood cell survival by increasing ATP and diminishes sickling by decreasing 2,3-diphosphoglycerate. We aimed to evaluate the efficacy and safety of mitapivat in patients with sickle cell disease.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We report results from the phase 2, 12-week, double-blind period of RISE UP, a global, phase 2/3, double-blind, randomised, placebo-controlled trial. The phase 2 part of the study was conducted at 32 clinical study sites across 13 countries. Patients aged 16 years or older with a confirmed diagnosis of sickle cell disease (any genotype), baseline haemoglobin of 5·5-10·5 g/dL (inclusive), and two to ten sickle cell pain crises within 12 months before providing informed consent, were randomly assigned 1:1:1 to receive oral mitapivat 50 mg, 100 mg, or placebo twice daily, in this portion of the study which is now complete. Randomisation was performed using a permuted-block method and concealed with an interactive response system; patients, investigators, and individuals assessing outcomes were masked to treatment assignment. Primary efficacy and safety endpoints were haemoglobin response (≥1·0 g/dL increase from baseline in average haemoglobin concentration from week 10 through week 12), and type, severity, and relationship to study drug of adverse and serious adverse events. Efficacy and safety endpoints were evaluated in the full analysis set (all randomly assigned patients) and safety analysis set (all patients who received at least one dose of study drug), respectively. This study is registered with ClinicalTrials.gov as part of an ongoing phase 2/3 study (NCT05031780).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Between Jan 19, 2022, and April 25, 2023, 79 patients were randomly assigned (51 [65%] female, 28 [35%] male; 46 [58%] Black or African American, 26 [33%] White, five [6%] multiracial, two [3%] Asian); 26 received mitapivat 50 mg, 26 received mitapivat 100 mg, and 27 received placebo, twice daily. Both treatment groups showed a statistically significant haemoglobin response rate versus placebo (12 [46%] of 26 patients in the mitapivat 50 mg group and 13 [50%] of 26 patients in the mitapivat 100 mg group, versus one [4%] of 27 patients in the placebo group; two-sided p=0·0003 and p=0·0001, respectively). Mitapivat was generally well tolerated. Serious adverse events were reported in two (8%) of 26 patients in the mitapivat 50 mg group, four (15%) of 26 patients in the mitapivat 100 mg group, and three (11%) of 27 patients in the placebo group; grade 3 or worse adverse events occurred in three (12%), five (19%), and two (7%) patients, respectively. No serious or grade 3 or worse adverse events were considered treatment related and there were no treatment-related deaths. The mo","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e35-e44"},"PeriodicalIF":15.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792640","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}

{"title":"Re-energising therapy options in sickle cell disease: the mitapivat phase 2 trial results.","authors":"Parul Rai, Jane S Hankins","doi":"10.1016/S2352-3026(24)00378-8","DOIUrl":"https://doi.org/10.1016/S2352-3026(24)00378-8","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"12 1","pages":"e5-e6"},"PeriodicalIF":15.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933199","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}

{"title":"Patient-reported outcomes following ciltacabtagene autoleucel or standard of care in patients with lenalidomide-refractory multiple myeloma (CARTITUDE-4): results from a randomised, open-label, phase 3 trial.","authors":"Roberto Mina, Anne K Mylin, Hisayuki Yokoyama, Hila Magen, Winfried Alsdorf, Monique C Minnema, Leyla Shune, Iris Isufi, Simon J Harrison, Urvi A Shah, Jordan M Schecter, Martin Vogel, Nikoletta Lendvai, Katharine S Gries, Eva G Katz, Ana Slaughter, Carolina Lonardi, Jane Gilbert, Quanlin Li, William Deraedt, Octavio Costa Filho, Nitin Patel, Erika Florendo, Lionel Karlin, Katja Weisel","doi":"10.1016/S2352-3026(24)00320-X","DOIUrl":"https://doi.org/10.1016/S2352-3026(24)00320-X","url":null,"abstract":"<p><strong>Background: </strong>In CARTITUDE-4, ciltacabtagene autoleucel (cilta-cel) significantly improved progression-free survival (primary endpoint; previously reported) versus standard of care in patients with relapsed, lenalidomide-refractory multiple myeloma. We report here patient-reported outcomes.</p><p><strong>Methods: </strong>In the ongoing, phase 3, open-label CARTITUDE-4 study, patients were recruited from 81 sites in the USA, Europe, Asia, and Australia, and were randomly assigned 1:1 to cilta-cel (target, 0·75 × 10⁶ CAR-T cells/kg) or standard of care (daratumumab, pomalidomide, and dexamethasone; pomalidomide, bortezomib, and dexamethasone). Eligible patients had relapsed, lenalidomide-refractory multiple myeloma, received one to three previous treatment lines including a proteasome inhibitor and an immunomodulatory drug, and had an ECOG performance status of 0 or 1. Secondary endpoints reported here include time to sustained worsening of symptoms (Multiple Myeloma Symptom and Impact Questionnaire [MySIm-Q]; a key secondary endpoint) and change in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire Core C30 (intention-to-treat population) and EuroQol 5-Dimension 5-Level (EQ-5D-5L; intention-to-treat population). This study is registered with ClinicalTrials.gov number NCT04181827 and is ongoing.</p><p><strong>Findings: </strong>Patients were enrolled from July 10, 2020, to Nov 17, 2021, and 419 of 516 screened patients were randomly assigned (cilta-cel, n=208; standard of care, n=211; median follow-up, 15·9 months [IQR 12·4 to 17·8]); median age was 61 years. 191 (92%) of 208 patients in the cilta-cel group and 190 (91%) of 209 evaluable patients in the standard- of-care group completed baseline assessments. MySIm-Q compliance post-baseline was 70 to 81% (cilta-cel) and 79 to 89% (standard of care). MySIm-Q median time to sustained symptom worsening with cilta-cel versus standard of care was 23·7 versus 18·9 months (HR 0·42; 95% CI 0·26 to 0·68). 12-month mean changes for EORTC global health status (GHS) were +10·1 (95% CI 7·0 to 13·1) and -1·5 (95% CI -5·3 to 2·3) points and were +8·0 (95% CI 5·2 to 10·7) and +1·4 (95% CI -1·9 to 4·7) points for EQ-5D-5L visual analogue scale (VAS). Rates of clinically meaningful improvements in GHS and VAS were higher with cilta-cel than with standard of care.</p><p><strong>Interpretation: </strong>Health-related QoL improvements and delayed symptom worsening support cilta-cel's clinical efficacy in lenalidomide-refractory disease.</p><p><strong>Funding: </strong>Janssen Research & Development, Legend Biotech USA.</p>","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"12 1","pages":"e45-e56"},"PeriodicalIF":15.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933198","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}

{"title":"Haematology and climate change.","authors":"The Lancet Haematology","doi":"10.1016/S2352-3026(24)00381-8","DOIUrl":"https://doi.org/10.1016/S2352-3026(24)00381-8","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"12 1","pages":"e1"},"PeriodicalIF":15.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933195","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}

{"title":"Correction to Lancet Haematol 2024; published online Dec 4. https://doi.org/10.1016/S2352-3026(24)00319-3.","authors":"","doi":"10.1016/S2352-3026(24)00382-X","DOIUrl":"10.1016/S2352-3026(24)00382-X","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e9"},"PeriodicalIF":15.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824559","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}

{"title":"Air pollution and venous thromboembolism: current knowledge and future perspectives.","authors":"Dawn Swan, Robert Turner, Massimo Franchini, Pier Mannuccio Mannucci, Jecko Thachil","doi":"10.1016/S2352-3026(24)00291-6","DOIUrl":"10.1016/S2352-3026(24)00291-6","url":null,"abstract":"<p><p>Air pollution, comprising a variable mixture of gaseous and solid particulate material, represents a serious, unmet, global health issue. The Global Burden of Disease study reported that 12% of all deaths occurring in 2019 were related to ambient air pollution, with particulate matter often considered to be the leading cause of harm. As of 2024, over 90% of the world's population are exposed to excessive amounts of particulate matter, based on WHO maximum exposure level guidelines. A substantial body of evidence supports a link between air pollution and cardiovascular disease, with around half of ambient pollution-related deaths thought to be secondary to cardiovascular causes. A possible association between particulate matter and venous thromboembolism has been less clear, but in the past decade, several studies have added to the available literature. In this Review, we discuss the current epidemiological evidence linking air pollution to the development of venous thrombotic events. We consider mechanisms promoting a thromboinflammatory phenotype in these individuals, including platelet dysfunction, dysregulated fibrinolysis, and enhanced thrombin generation. Given the relevance to global health, we also discuss possible strategies required to mitigate the impact of air pollution on human health worldwide.</p>","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e68-e82"},"PeriodicalIF":15.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802846","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}