Pub Date : 2025-10-08DOI: 10.1016/s2352-3026(25)00254-6
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
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.
{"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}
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.
背景：复发或难治性多发性骨髓瘤仍然无法治愈。CT071是一种完全的人自体嵌合抗原受体（CAR） t细胞疗法，靶向G蛋白偶联受体C类5组成员D (GPRC5D)，正在加速生产。该试验旨在评估CT071在复发或难治性多发性骨髓瘤中的初步活性、安全性和细胞动力学。方法：这项首次人体、单中心、单臂、1期研究在中国上海长征医院进行。符合条件的患者是年龄在18岁或以上的复发或难治性多发性骨髓瘤患者，既往接受过三条或更多的治疗，包括蛋白酶体抑制剂和免疫调节剂，或接受过双级难治治疗，并且在最后一条治疗线上疾病进展。要求东部肿瘤合作组业绩状态0-2。患者以每公斤0.1 × 106 CAR - T细胞或每公斤0.3 × 106 CAR - T细胞的剂量接受CT071治疗，主要终点是安全性，包括剂量限制性毒性、不良事件和剂量确定。活动度也作为次要终点进行评估。所有接受CT071治疗的患者均被纳入安全性和活动性分析。该试验已在ClinicalTrials.gov注册（NCT05838131），注册已完成。在2023年4月28日至2024年6月21日期间，23名患者入组并接受了单采术。3例患者在单采后被排除（1例因疾病进展迅速而停药，1例因活动性感染而停药，1例因CAR - T细胞制造失败而停药），共输注20例患者。中位年龄为66.3岁（IQR为53.0 ~ 65.5）。20例患者中男性12例（60%），女性8例（40%）；所有患者均为中国人。中位随访时间为10.71个月（IQR为6.13 ~ 12.02）。没有观察到剂量限制性毒性，推荐的2期剂量为每公斤0.1 × 106个CAR - T细胞。血液学毒性是最常见的3级或更严重的治疗相关不良事件，发生在所有患者中。20例患者中有12例（60%）发生细胞因子释放综合征，均为1-2级。1例（5%）患者有3级免疫效应细胞相关神经毒性综合征。7例（35%）患者报告了严重的治疗相关不良事件；无治疗相关死亡发生。皮肤相关事件包括4例（20%）患者的甲变，1例（5%）患者的皮疹，均为1级。客观缓解率为100% (95% CI 83·2-100)，完全缓解或更好率为50%（20例患者中有10例）。ct071在复发或难治性多发性骨髓瘤患者中表现出令人鼓舞的安全性和令人信服的活性。国家自然科学基金，上海市医院发展中心临床研究计划。
{"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}
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
{"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}
Pub Date : 2025-09-18DOI: 10.1016/s2352-3026(25)00260-1
The Lancet Haematology
{"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}
Pub Date : 2025-09-18DOI: 10.1016/s2352-3026(25)00235-2
Rutendo Muzambi,Alex Bottle,Daniel Dexter,Cherelle Augustine,Jeannine Joseph,Funmi Dasaolu,Siobhán B Carr,Carl Reynolds,Ganesh Sathyamoorthy,John James,Frédéric B Piel
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.
镰状细胞病是英国最常见的遗传病之一，常被认为是一种被忽视的疾病，但支持这一观点的严格定量证据很少。多种情况的比较研究提供了记录不平等和指导公共卫生政策的有效途径。因此，我们旨在比较英国镰状细胞病、囊性纤维化和血友病的研究和资金不平等指标。方法：在这项描述性比较研究中，我们收集了镰状细胞病、囊性纤维化和血友病患病率的公开数据，以及7项比较指标：英国公共卫生研究资助者（惠康信托基金、国家卫生与护理研究所和英国研究与创新研究所）的资助数量和价值；专门慈善机构可利用的资源（镰状细胞协会、囊性纤维化信托基金会和血友病协会）；疾病登记的特征（国家血红蛋白病登记、英国囊性纤维化登记和英国国家血友病数据库）；注册临床试验的数量（国家医学临床试验图书馆和欧盟临床试验注册）；科学出版物数量（PubMed）；药物批准数量（药品和保健产品监管机构）；以及在线疾病意识（b谷歌Trends and Glimpse）。我们进行了描述性分析，包括计数、比例、均值和比率。研究结果我们发现所考虑的七个指标存在显著差异。镰状细胞病通常是最被忽视的疾病，特别是考虑到受影响的人数时。囊性纤维化的人均年研究经费（704英镑[95% CI 697-710]）几乎是镰状细胞病（184英镑[172-196]）的四倍，是血友病（315英镑[226-404]）的两倍。每273名镰状细胞病患者中有一项临床试验，而囊性纤维化和血友病患者分别为每53人和55人进行一项临床试验。囊性纤维化的平均年发表数（2431篇）几乎是镰状细胞病（1359篇）或血友病（1193篇）的两倍。解释：比较证据支持镰状细胞病与囊性纤维化和血友病相比在英国的研究和资助方面被忽视的观点。每项指标的最高值，通常在囊性纤维化中观察到，为其他两种情况提供了基准目标。更多的专门研究经费可能会对其他指标产生连锁反应，从而可以指导公共卫生政策，并对镰状细胞病患者的生活质量产生重大影响。资助nhs种族和健康观察站。
{"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}
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
本达莫司汀和利妥昔单抗联合中剂量阿糖胞苷（RBAC）是老年、健康的套细胞淋巴瘤患者的标准初始治疗方案之一。我们的目的是研究在RBAC中加入venetoclax是否会改善高风险套细胞淋巴瘤患者的无进展生存期。方法fil_v - rbac是一项多中心、单臂、2期研究，在意大利Linfomi基金会的35家机构进行。组织学诊断为套细胞淋巴瘤的未接受治疗的患者，年龄≥65岁，符合意大利基金会Linfomi修订的老年综合评估（或年龄小于65岁，不适合大剂量化疗，东部肿瘤合作组表现状态为2或以下），入组后根据囊细胞形态的存在，Ki67 30%或更高，TP53，或者17p缺失。低风险患者每4周静脉注射RBAC（利妥昔单抗375 mg/m2，第1天；苯达莫司汀70 mg/m2，第1天和第2天；阿糖胞苷500 mg/m2，第1、2和3天），共6个周期。高风险患者接受4个周期的RBAC，随后是固定时间的口服venetoclax巩固（4个月，800 mg/天）和维持（20个月，400 mg/天）。主要终点是接受至少一剂RBAC的高风险患者的2年无进展生存期。该试验已在ClinicalTrials.gov注册，注册号为NCT03567876，这是最终报告。在2018年9月10日至2021年7月26日期间，155名患者被筛选纳入研究，其中140名患者入组并进行了研究终点分析。中位年龄为72岁（IQR 69-76），男性107例（76%），女性33例（24%），均为White。54例（39%）患者为高危型（TP53突变28例[20%]，17p缺失19例[14%]，Ki67≥30% 34例[24%]，囊胚形态13例[9%]），86例（61%）为低危型。中位随访45个月（IQR 40-55）后，高危组2年无进展生存期为60% (95% CI 48-74)，中位无进展生存期为37个月（95% CI 19-未达到）。在venetoclax巩固期间最常见的3级或更严重的不良事件是中性粒细胞减少（43例患者中有12例[28%]），其次是血小板减少（3例[7%]）和皮肤反应（3例[7%]）。在venetoclax维持期间，最常见的3级或更严重不良事件是中性粒细胞减少症（37例患者中有7例[19%]），其次是血小板减少症（2例[5%]）和贫血（2例[5%]）。140例患者中有1例（1%）出现治疗相关死亡（高风险患者首次RBAC诱导时肿瘤溶解综合征）。解释：据我们所知，这是第一个根据风险情况对套细胞淋巴瘤患者进行分层治疗的前瞻性研究。我们的研究结果表明，在高风险疾病患者中，添加固定时间的venetoclax可改善RBAC的性能。我们的研究结果指出了在初始诊断时识别高风险疾病患者的重要性。资助：意大利linformi - ente del Terzo Settore基金会、白血病和淋巴瘤协会、意大利卫生部和艾伯维。翻译摘要的意大利语翻译见补充资料部分。
{"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}
Pub Date : 2025-09-16DOI: 10.1016/s2352-3026(25)00204-2
Bingwen Eugene Fan,Kevin Milla,Scott McAlister,Brandon Jin An Ong,Sam Schulman,Roopen Arya,Helen Okoye,Suely Meireles Rezende,Giuseppe Lippi,Leonardo Pasalic,Bian Hong Wang,Ming Sheng Lim,Yen Lin Chee,Amanda Zain,Jeannie Su Hui Tey,Emmanuel J Favaloro
This Viewpoint issues a multidisciplinary call to embed sustainability into anticoagulation care, aligning clinical excellence with climate responsibility. Anticoagulation management-including drug manufacturing, laboratory diagnostics, therapeutic monitoring, and long-term follow-up-contributes substantially to health-care-associated carbon emissions. We propose a systems-level decarbonisation strategy, anchored in life cycle assessment methodology, to quantify emissions across anticoagulation care and identify high-impact intervention points. Core strategies include reducing unnecessary laboratory testing, greening laboratory operations through recyclable consumables and energy-efficient infrastructure, transitioning to lower-carbon anticoagulants, and promoting antithrombotic stewardship to reduce dosing errors and drug waste. Digital health technologies, such as telemedicine, artificial intelligence, and mobile apps, are positioned as enablers of low-emission, patient-centred care. Circular economy principles and carbon-informed procurement are integrated into the therapeutic pathway, supported by policy levers that incentivise sustainable practices. Finally, we call for inclusive engagement of low-income and middle-income country stakeholders to ensure equitable, scalable, and context-appropriate implementation of climate-resilient thrombosis care.
{"title":"Sustainable anticoagulation for climate resilient care.","authors":"Bingwen Eugene Fan,Kevin Milla,Scott McAlister,Brandon Jin An Ong,Sam Schulman,Roopen Arya,Helen Okoye,Suely Meireles Rezende,Giuseppe Lippi,Leonardo Pasalic,Bian Hong Wang,Ming Sheng Lim,Yen Lin Chee,Amanda Zain,Jeannie Su Hui Tey,Emmanuel J Favaloro","doi":"10.1016/s2352-3026(25)00204-2","DOIUrl":"https://doi.org/10.1016/s2352-3026(25)00204-2","url":null,"abstract":"This Viewpoint issues a multidisciplinary call to embed sustainability into anticoagulation care, aligning clinical excellence with climate responsibility. Anticoagulation management-including drug manufacturing, laboratory diagnostics, therapeutic monitoring, and long-term follow-up-contributes substantially to health-care-associated carbon emissions. We propose a systems-level decarbonisation strategy, anchored in life cycle assessment methodology, to quantify emissions across anticoagulation care and identify high-impact intervention points. Core strategies include reducing unnecessary laboratory testing, greening laboratory operations through recyclable consumables and energy-efficient infrastructure, transitioning to lower-carbon anticoagulants, and promoting antithrombotic stewardship to reduce dosing errors and drug waste. Digital health technologies, such as telemedicine, artificial intelligence, and mobile apps, are positioned as enablers of low-emission, patient-centred care. Circular economy principles and carbon-informed procurement are integrated into the therapeutic pathway, supported by policy levers that incentivise sustainable practices. Finally, we call for inclusive engagement of low-income and middle-income country stakeholders to ensure equitable, scalable, and context-appropriate implementation of climate-resilient thrombosis care.","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"67 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089806","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}
Pub Date : 2025-09-14DOI: 10.1016/s2352-3026(25)00228-5
Eric Tse,Christiane Querfeld,Kenji Ishitsuka,Yok-Lam Kwong
Mature T-cell and natural killer-cell neoplasms are a heterogenous group of uncommon lymphomas. Conventional therapy with mainly cytotoxic chemotherapy for this subgroup is suboptimal, and the treatment outcome is unsatisfactory. With the advances in the understanding of disease biology, considerable progress has been made in recent years. Monoclonal antibodies or antibody-drug conjugates targeting T-cell lymphoma surface antigens have been approved, including brentuximab vedotin, for the treatment of CD30-positive nodal and cutaneous T-cell lymphoma, and mogamulizumab, for mycosis fungoides and adult T-cell leukaemia/lymphoma. Furthermore, immune checkpoint blockade has also shown promise in the management of mycosis fungoides and extranodal natural killer/T-cell lymphoma. Epigenetic dysregulation is frequently found in mature T-cell and natural killer-cell lymphomas; hence, therapeutic agents acting on epigenetic regulators, such as histone deacetylase inhibitors, have been tested in clinical trials with promising results. Novel approaches including cell therapy and adoptive immunotherapy are currently being evaluated. In this Series paper, we discuss the limitations of the conventional treatment options and the use of these novel approaches for mature T-cell and natural killer-cell lymphomas.
{"title":"Emerging therapeutic strategies for mature T-cell and natural killer-cell lymphomas.","authors":"Eric Tse,Christiane Querfeld,Kenji Ishitsuka,Yok-Lam Kwong","doi":"10.1016/s2352-3026(25)00228-5","DOIUrl":"https://doi.org/10.1016/s2352-3026(25)00228-5","url":null,"abstract":"Mature T-cell and natural killer-cell neoplasms are a heterogenous group of uncommon lymphomas. Conventional therapy with mainly cytotoxic chemotherapy for this subgroup is suboptimal, and the treatment outcome is unsatisfactory. With the advances in the understanding of disease biology, considerable progress has been made in recent years. Monoclonal antibodies or antibody-drug conjugates targeting T-cell lymphoma surface antigens have been approved, including brentuximab vedotin, for the treatment of CD30-positive nodal and cutaneous T-cell lymphoma, and mogamulizumab, for mycosis fungoides and adult T-cell leukaemia/lymphoma. Furthermore, immune checkpoint blockade has also shown promise in the management of mycosis fungoides and extranodal natural killer/T-cell lymphoma. Epigenetic dysregulation is frequently found in mature T-cell and natural killer-cell lymphomas; hence, therapeutic agents acting on epigenetic regulators, such as histone deacetylase inhibitors, have been tested in clinical trials with promising results. Novel approaches including cell therapy and adoptive immunotherapy are currently being evaluated. In this Series paper, we discuss the limitations of the conventional treatment options and the use of these novel approaches for mature T-cell and natural killer-cell lymphomas.","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145077724","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}
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