Pub Date : 2025-04-01DOI: 10.1016/S2352-3026(24)00398-3
Ruben Van Dijck, John-John Schnog, Peter Te Boekhorst
{"title":"Fedratinib for patients with myelofibrosis.","authors":"Ruben Van Dijck, John-John Schnog, Peter Te Boekhorst","doi":"10.1016/S2352-3026(24)00398-3","DOIUrl":"10.1016/S2352-3026(24)00398-3","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"12 4","pages":"e240"},"PeriodicalIF":15.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-01DOI: 10.1016/S2352-3026(25)00010-9
Claire N Harrison, Patrick Brown, Jean-Jacques Kiladjian
{"title":"Fedratinib for patients with myelofibrosis - Authors' reply.","authors":"Claire N Harrison, Patrick Brown, Jean-Jacques Kiladjian","doi":"10.1016/S2352-3026(25)00010-9","DOIUrl":"10.1016/S2352-3026(25)00010-9","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"12 4","pages":"e241-e242"},"PeriodicalIF":15.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-01DOI: 10.1016/S2352-3026(25)00032-8
Charles J Milrod, Lila Rubin, Boris Martinez, Thomas A Ollila, Adam J Olszewski, Ari Pelcovits
Indolent lymphomas are generally incurable, with protracted disease courses. The approval of drug treatment options often relies on surrogate endpoints (eg, progression-free survival), which do not capture patient-centred outcomes such as quality of life (QOL). This systematic review characterises the use of QOL as an endpoint in randomised controlled trials (RCTs) of indolent lymphomas, and the association of QOL with survival outcomes. ClinicalTrials.gov was searched from database inception to May 20, 2024, for phase 3 RCTs of indolent lymphomas, including follicular lymphoma, marginal zone lymphoma, chronic lymphocytic leukaemia or small lymphocytic lymphoma, gastric mucosa-associated lymphoid tissue lymphoma, and Waldenström macroglobulinaemia. 103 RCTs met eligibility criteria. Data on QOL endpoints were collected in 53 (51%) of 103 trials, but reported in only 25 (24%). Improvements in QOL was reported in 11 (44%) of these RCTs, and these trials were more likely to show progression-free survival and overall survival benefits. We found that trials with neutral or worsened QOL outcomes often framed the results positively, presenting QOL data as supporting treatment use. This systematic review highlights that data on QOL endpoints are undercollected, under-reported, and often positively framed despite a lack of improvement, underscoring the need for transparent QOL reporting to enhance patient-centred care.
惰性淋巴瘤通常无法治愈，病程漫长。药物治疗方案的批准往往依赖于替代终点（如无进展生存期），而替代终点并不能反映以患者为中心的结果，如生活质量（QOL）。本系统性综述介绍了将生活质量作为终点用于非淋巴瘤随机对照试验（RCT）的情况，以及生活质量与生存结果之间的关系。临床试验网（ClinicalTrials.gov）检索了从数据库建立之初到2024年5月20日期间进行的3期临床试验，包括滤泡淋巴瘤、边缘区淋巴瘤、慢性淋巴细胞白血病或小淋巴细胞淋巴瘤、胃黏膜相关淋巴组织淋巴瘤和瓦尔登斯特伦巨球蛋白血症。103项研究性试验符合资格标准。103 项试验中有 53 项（51%）收集了 QOL 终点数据，但只有 25 项（24%）进行了报告。在这些研究中，有 11 项（44%）报告了 QOL 的改善情况，这些试验更有可能显示出无进展生存期和总生存期的益处。我们发现，QOL结果为中性或恶化的试验通常会对结果进行正面描述，将QOL数据作为支持治疗的依据。本系统综述强调，有关 QOL 终点的数据收集不足、报告不足，而且尽管缺乏改善，却往往被正面描述，这突出表明有必要进行透明的 QOL 报告，以加强以患者为中心的护理。
{"title":"Quality-of-life endpoints collection, reporting, and framing in randomised trials of indolent lymphomas: a systematic review.","authors":"Charles J Milrod, Lila Rubin, Boris Martinez, Thomas A Ollila, Adam J Olszewski, Ari Pelcovits","doi":"10.1016/S2352-3026(25)00032-8","DOIUrl":"10.1016/S2352-3026(25)00032-8","url":null,"abstract":"<p><p>Indolent lymphomas are generally incurable, with protracted disease courses. The approval of drug treatment options often relies on surrogate endpoints (eg, progression-free survival), which do not capture patient-centred outcomes such as quality of life (QOL). This systematic review characterises the use of QOL as an endpoint in randomised controlled trials (RCTs) of indolent lymphomas, and the association of QOL with survival outcomes. ClinicalTrials.gov was searched from database inception to May 20, 2024, for phase 3 RCTs of indolent lymphomas, including follicular lymphoma, marginal zone lymphoma, chronic lymphocytic leukaemia or small lymphocytic lymphoma, gastric mucosa-associated lymphoid tissue lymphoma, and Waldenström macroglobulinaemia. 103 RCTs met eligibility criteria. Data on QOL endpoints were collected in 53 (51%) of 103 trials, but reported in only 25 (24%). Improvements in QOL was reported in 11 (44%) of these RCTs, and these trials were more likely to show progression-free survival and overall survival benefits. We found that trials with neutral or worsened QOL outcomes often framed the results positively, presenting QOL data as supporting treatment use. This systematic review highlights that data on QOL endpoints are undercollected, under-reported, and often positively framed despite a lack of improvement, underscoring the need for transparent QOL reporting to enhance patient-centred care.</p>","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"12 4","pages":"e312-e317"},"PeriodicalIF":15.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774702","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":"Establishment of a haematopoietic cell transplantation programme for children with sickle cell disease in Tanzania.","authors":"Fabio Giglio, Stella Malangahe, Shakilu Jumanne, Melikiard Mhozya, Alphonse Chandika, Cornelio Uderzo","doi":"10.1016/S2352-3026(24)00322-3","DOIUrl":"10.1016/S2352-3026(24)00322-3","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"12 4","pages":"e244-e245"},"PeriodicalIF":15.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01Epub Date: 2025-02-10DOI: 10.1016/S2352-3026(24)00376-4
Maria Domenica Cappellini, Vip Viprakasit, Pencho Georgiev, Thomas D Coates, Raffaella Origa, Abderrahim Khelif, Hong-Keng Liew, Adisak Tantiworawit, Lee-Ping Chew, Abdalla Khalil, P Joy Ho, Kevin H M Kuo, Natalia Holot, Martina Perin, Ana Carolina Giuseppi, Wen-Ling Kuo, Yinzhi Lai, Loyse Felber Medlin, Luciana Moro Bueno, Antonis Kattamis, Ali T Taher
<p><strong>Background: </strong>Treatments to reduce red blood cell (RBC) transfusion burden among patients with transfusion-dependent β-thalassaemia remain limited. Here, we report long-term follow-up data from the phase 3 BELIEVE trial of luspatercept for transfusion-dependent β-thalassaemia.</p><p><strong>Methods: </strong>BELIEVE was a phase 3, randomised, double-blind, placebo-controlled study performed at 65 sites in 15 countries. The trial included adults with transfusion-dependent β-thalassaemia or haemoglobin E/β-thalassaemia and Eastern Cooperative Oncology Group score of 0-1. Patients were randomly assigned (2:1) using integrated response technology stratified by region to luspatercept (1·0-1·25 mg/kg) or placebo administered subcutaneously once every 21 days. After study unblinding, patients could receive luspatercept in the open-label extension phase (crossover allowed). The primary endpoint results (proportion of patients with reduction in transfusion burden of ≥33% and ≥2 RBC units during weeks 13-24) are described elsewhere; herein we present an update to the primary endpoint analysis consequent to late-reported transfusion events. We also report long-term efficacy (intention-to-treat population) and safety data (safety population) for patients followed up for approximately 3 years. This trial is registered on ClinicalTrials.gov (NCT02604433) and is completed.</p><p><strong>Findings: </strong>Between May 2, 2016, and May 16, 2017, 336 patients were randomly assigned to luspatercept (n=224) or placebo (n=112). The median age of patients was 30 years (IQR 23-40); 195 (58%) were female and 141 (42%) male. As of Jan 5, 2021, the median duration of treatment in the luspatercept group was 153·6 weeks (IQR 81·0-171·0) and median study follow-up was 163·1 weeks (140·5-176·2). Due to the difference in treatment duration between the luspatercept and placebo groups, no comparative analyses between the two groups were performed after week 96. Patients in the luspatercept group showed a sustained reduction in RBC transfusion burden from baseline through week 192, with mean decreases of 6·2 RBC units (SD 5·7) during weeks 97-144 and 6·4 RBC units (4·3) during weeks 145-192. In the luspatercept group, a 33% or greater reduction in transfusion burden from baseline was observed in 173 (77%) patients over any 12-week interval and in 116 (52%) patients over any 24-week interval. The median total duration of 33% or greater transfusion burden reduction response during any period of at least 12 weeks was 586·0 days (IQR 264·0-1010·0). The most common grade 3 or worse treatment-emergent adverse events (TEAEs) among all patients who received luspatercept (n=315, including 92 patients who crossed over after study unblinding) were anaemia (nine [3%]), increased liver iron concentration (seven [2%]), and bone pain (seven [2%]); serious TEAEs occurred in 71 (23%) patients. No treatment-related deaths occurred in any group during the study.</p><p><strong>Inte
{"title":"Long-term efficacy and safety of luspatercept for the treatment of anaemia in patients with transfusion-dependent β-thalassaemia (BELIEVE): final results from a phase 3 randomised trial.","authors":"Maria Domenica Cappellini, Vip Viprakasit, Pencho Georgiev, Thomas D Coates, Raffaella Origa, Abderrahim Khelif, Hong-Keng Liew, Adisak Tantiworawit, Lee-Ping Chew, Abdalla Khalil, P Joy Ho, Kevin H M Kuo, Natalia Holot, Martina Perin, Ana Carolina Giuseppi, Wen-Ling Kuo, Yinzhi Lai, Loyse Felber Medlin, Luciana Moro Bueno, Antonis Kattamis, Ali T Taher","doi":"10.1016/S2352-3026(24)00376-4","DOIUrl":"10.1016/S2352-3026(24)00376-4","url":null,"abstract":"<p><strong>Background: </strong>Treatments to reduce red blood cell (RBC) transfusion burden among patients with transfusion-dependent β-thalassaemia remain limited. Here, we report long-term follow-up data from the phase 3 BELIEVE trial of luspatercept for transfusion-dependent β-thalassaemia.</p><p><strong>Methods: </strong>BELIEVE was a phase 3, randomised, double-blind, placebo-controlled study performed at 65 sites in 15 countries. The trial included adults with transfusion-dependent β-thalassaemia or haemoglobin E/β-thalassaemia and Eastern Cooperative Oncology Group score of 0-1. Patients were randomly assigned (2:1) using integrated response technology stratified by region to luspatercept (1·0-1·25 mg/kg) or placebo administered subcutaneously once every 21 days. After study unblinding, patients could receive luspatercept in the open-label extension phase (crossover allowed). The primary endpoint results (proportion of patients with reduction in transfusion burden of ≥33% and ≥2 RBC units during weeks 13-24) are described elsewhere; herein we present an update to the primary endpoint analysis consequent to late-reported transfusion events. We also report long-term efficacy (intention-to-treat population) and safety data (safety population) for patients followed up for approximately 3 years. This trial is registered on ClinicalTrials.gov (NCT02604433) and is completed.</p><p><strong>Findings: </strong>Between May 2, 2016, and May 16, 2017, 336 patients were randomly assigned to luspatercept (n=224) or placebo (n=112). The median age of patients was 30 years (IQR 23-40); 195 (58%) were female and 141 (42%) male. As of Jan 5, 2021, the median duration of treatment in the luspatercept group was 153·6 weeks (IQR 81·0-171·0) and median study follow-up was 163·1 weeks (140·5-176·2). Due to the difference in treatment duration between the luspatercept and placebo groups, no comparative analyses between the two groups were performed after week 96. Patients in the luspatercept group showed a sustained reduction in RBC transfusion burden from baseline through week 192, with mean decreases of 6·2 RBC units (SD 5·7) during weeks 97-144 and 6·4 RBC units (4·3) during weeks 145-192. In the luspatercept group, a 33% or greater reduction in transfusion burden from baseline was observed in 173 (77%) patients over any 12-week interval and in 116 (52%) patients over any 24-week interval. The median total duration of 33% or greater transfusion burden reduction response during any period of at least 12 weeks was 586·0 days (IQR 264·0-1010·0). The most common grade 3 or worse treatment-emergent adverse events (TEAEs) among all patients who received luspatercept (n=315, including 92 patients who crossed over after study unblinding) were anaemia (nine [3%]), increased liver iron concentration (seven [2%]), and bone pain (seven [2%]); serious TEAEs occurred in 71 (23%) patients. No treatment-related deaths occurred in any group during the study.</p><p><strong>Inte","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e180-e189"},"PeriodicalIF":15.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01Epub Date: 2025-02-04DOI: 10.1016/S2352-3026(24)00372-7
Sijian Yu, Fen Huang, Na Xu, Zhongming Zhang, Can Liu, Xiaojun Xu, Zhiping Fan, Xiangzong Zeng, Qiong Liu, Guo Qiu, Xu Xi, Ren Lin, Xinquan Liang, Yirong Jiang, Min Dai, Hua Jin, Xiaofang Li, Shunqing Wang, Meiqing Wu, Jing Sun, Li Xuan, Qifa Liu
<p><strong>Background: </strong>Retrospective studies suggested that haploidentical transplantation combined with unrelated cord blood might improve survival for patients with haematological malignancies. We aimed to assess whether transplantation of haploidentical peripheral blood stem cells (PBSCs) plus unrelated cord blood would achieve superior disease-free survival compared with transplantation of haploidentical PBSCs plus bone marrow in this population.</p><p><strong>Methods: </strong>We did an open-label, randomised, phase 3 trial at seven hospitals in China. Eligible patients (aged 18-65 years) had a diagnosis of haematological malignancy, an Eastern Cooperative Oncology Group performance status of 0-2 and transplant comorbidity index of 0-2, and were receiving their first allogenic haematopoietic stem cell transplant. Patients were randomly assigned (1:1) to receive transplantation of haploidentical PBSCs plus bone marrow or haploidentical PBSCs plus unrelated cord blood. The primary endpoint was 1-year disease-free survival. All efficacy and safety endpoints were assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT05290545) and is complete.</p><p><strong>Findings: </strong>Between March 5, 2022, and Jan 2, 2023, 357 participants were screened for eligibility, and 314 were randomly assigned to receive transplantation of haploidentical PBSCs plus unrelated cord blood (n=157) or haploidentical PBSCs plus bone marrow (n=157). Median follow-up was 17·2 months (IQR 10·0-20·8) after random assignment. 1-year disease-free survival was 82·2% (95% CI 75·2-87·3) in the group receiving haploidentical PBSCs plus unrelated cord blood (PBSCs plus unrelated cord blood group) and 65·6% (57·6-72·5) in the group receiving haploidentical PBSCs plus bone marrow ([PBSCs plus bone marrow group] hazard ratio [HR] 0·47, 95% CI 0·30-0·74; p=0·0010). The most common grade 3-5 adverse events within 100 days of transplantation in participants in the PBSCs plus unrelated cord blood and PBSCs plus bone marrow groups were infections (58 [37%] of 157 vs 77 [49%] of 157, p=0·030), acute graft-versus-host disease (49 [31%] vs 61 [39%]), and gastrointestinal disorders (38 [24%] vs 38 [24%]). Seven (4%) patients in the PBSCs plus unrelated cord blood group and 17 (11%) in the PBSCs plus bone marrow group died of transplantation-related causes within 100 days of transplantation. Causes of deaths in the PBSCs plus unrelated cord blood group versus the PBSCs plus bone marrow group included infections (four [3%] vs 11 [7%]), acute graft-versus-host disease (one [1%] vs three [2%]), vascular disorders (two [1%] vs one [1%]), cardiac disorders (none vs one [1%]), and respiratory disorders (none vs one [1%]).</p><p><strong>Interpretation: </strong>Transplantation of haploidentical PBSCs plus unrelated cord blood achieved superior 1-year disease-free survival compared with transplantation of haploidentical PBSCs plus bone marrow in p
{"title":"Haploidentical peripheral blood stem cells combined with bone marrow or unrelated cord blood as grafts for haematological malignancies: an open-label, multicentre, randomised, phase 3 trial.","authors":"Sijian Yu, Fen Huang, Na Xu, Zhongming Zhang, Can Liu, Xiaojun Xu, Zhiping Fan, Xiangzong Zeng, Qiong Liu, Guo Qiu, Xu Xi, Ren Lin, Xinquan Liang, Yirong Jiang, Min Dai, Hua Jin, Xiaofang Li, Shunqing Wang, Meiqing Wu, Jing Sun, Li Xuan, Qifa Liu","doi":"10.1016/S2352-3026(24)00372-7","DOIUrl":"10.1016/S2352-3026(24)00372-7","url":null,"abstract":"<p><strong>Background: </strong>Retrospective studies suggested that haploidentical transplantation combined with unrelated cord blood might improve survival for patients with haematological malignancies. We aimed to assess whether transplantation of haploidentical peripheral blood stem cells (PBSCs) plus unrelated cord blood would achieve superior disease-free survival compared with transplantation of haploidentical PBSCs plus bone marrow in this population.</p><p><strong>Methods: </strong>We did an open-label, randomised, phase 3 trial at seven hospitals in China. Eligible patients (aged 18-65 years) had a diagnosis of haematological malignancy, an Eastern Cooperative Oncology Group performance status of 0-2 and transplant comorbidity index of 0-2, and were receiving their first allogenic haematopoietic stem cell transplant. Patients were randomly assigned (1:1) to receive transplantation of haploidentical PBSCs plus bone marrow or haploidentical PBSCs plus unrelated cord blood. The primary endpoint was 1-year disease-free survival. All efficacy and safety endpoints were assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT05290545) and is complete.</p><p><strong>Findings: </strong>Between March 5, 2022, and Jan 2, 2023, 357 participants were screened for eligibility, and 314 were randomly assigned to receive transplantation of haploidentical PBSCs plus unrelated cord blood (n=157) or haploidentical PBSCs plus bone marrow (n=157). Median follow-up was 17·2 months (IQR 10·0-20·8) after random assignment. 1-year disease-free survival was 82·2% (95% CI 75·2-87·3) in the group receiving haploidentical PBSCs plus unrelated cord blood (PBSCs plus unrelated cord blood group) and 65·6% (57·6-72·5) in the group receiving haploidentical PBSCs plus bone marrow ([PBSCs plus bone marrow group] hazard ratio [HR] 0·47, 95% CI 0·30-0·74; p=0·0010). The most common grade 3-5 adverse events within 100 days of transplantation in participants in the PBSCs plus unrelated cord blood and PBSCs plus bone marrow groups were infections (58 [37%] of 157 vs 77 [49%] of 157, p=0·030), acute graft-versus-host disease (49 [31%] vs 61 [39%]), and gastrointestinal disorders (38 [24%] vs 38 [24%]). Seven (4%) patients in the PBSCs plus unrelated cord blood group and 17 (11%) in the PBSCs plus bone marrow group died of transplantation-related causes within 100 days of transplantation. Causes of deaths in the PBSCs plus unrelated cord blood group versus the PBSCs plus bone marrow group included infections (four [3%] vs 11 [7%]), acute graft-versus-host disease (one [1%] vs three [2%]), vascular disorders (two [1%] vs one [1%]), cardiac disorders (none vs one [1%]), and respiratory disorders (none vs one [1%]).</p><p><strong>Interpretation: </strong>Transplantation of haploidentical PBSCs plus unrelated cord blood achieved superior 1-year disease-free survival compared with transplantation of haploidentical PBSCs plus bone marrow in p","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e190-e200"},"PeriodicalIF":15.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371178","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号