Pub Date : 2025-06-13DOI: 10.1016/s2352-3026(25)00173-5
The Lancet Haematology
{"title":"Much to hope for in blood donation","authors":"The Lancet Haematology","doi":"10.1016/s2352-3026(25)00173-5","DOIUrl":"https://doi.org/10.1016/s2352-3026(25)00173-5","url":null,"abstract":"","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"51 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144305108","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 : 2025-05-16DOI: 10.1016/s2352-3026(25)00080-8
Omran Saifi,Chelsea C Pinnix,Chris R Kelsey,Leslie K Ballas,Sarah A Milgrom,Ranjana Advani,Margaret T Kasner,Stella Flampouri,Stephanie A Terezakis,Mark Sellmyer,John P Plastaras,Bradford S Hoppe
There has been a notable decrease in the use of radiation in lymphoma clinical practice and research in recent years. The NRG Hematologic Malignancies Working Group aimed to assess the inclusion of radiation oncology alongside haematology and oncology, pathology and molecular biology, and diagnostic radiology and nuclear medicine in lymphoma academic leadership positions. The haematology and oncology specialty had the highest representation among National Comprehensive Cancer Network lymphoma guideline committees, lymphoma research cooperative groups, lymphoma research foundations, and the editorial boards of seven high-impact haematology journals, with under-representation of radiation oncology and other specialties, such as diagnostic radiology and nuclear medicine. The NRG Hematologic Malignancies Working Group advocates for increased multidisciplinary representation and collaboration to enhance the quality of care and improve outcomes for patients with lymphoma.
{"title":"Radiate equity: the inclusion of radiation oncology and other specialties in lymphoma collaborative groups.","authors":"Omran Saifi,Chelsea C Pinnix,Chris R Kelsey,Leslie K Ballas,Sarah A Milgrom,Ranjana Advani,Margaret T Kasner,Stella Flampouri,Stephanie A Terezakis,Mark Sellmyer,John P Plastaras,Bradford S Hoppe","doi":"10.1016/s2352-3026(25)00080-8","DOIUrl":"https://doi.org/10.1016/s2352-3026(25)00080-8","url":null,"abstract":"There has been a notable decrease in the use of radiation in lymphoma clinical practice and research in recent years. The NRG Hematologic Malignancies Working Group aimed to assess the inclusion of radiation oncology alongside haematology and oncology, pathology and molecular biology, and diagnostic radiology and nuclear medicine in lymphoma academic leadership positions. The haematology and oncology specialty had the highest representation among National Comprehensive Cancer Network lymphoma guideline committees, lymphoma research cooperative groups, lymphoma research foundations, and the editorial boards of seven high-impact haematology journals, with under-representation of radiation oncology and other specialties, such as diagnostic radiology and nuclear medicine. The NRG Hematologic Malignancies Working Group advocates for increased multidisciplinary representation and collaboration to enhance the quality of care and improve outcomes for patients with lymphoma.","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097806","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}
BACKGROUNDRadiotherapy for indolent non-Hodgkin lymphoma has evolved to optimise the definitive dose while minimising toxicity. We aimed to assess the activity and safety of a hypofractionated low-dose radiotherapy regimen of 12 Gy in four fractions in patients with indolent non-Hodgkin lymphoma.METHODSThis multicentre, single-arm, phase 2 trial study enrolled patients from four hospitals in China. Patients aged 18 years or older with newly diagnosed or relapsed stage I-IV indolent non-Hodgkin lymphoma (follicular lymphoma, marginal zone lymphoma, and low-grade lymphoma) and an Eastern Cooperative Oncology Group performance status of 0-3 were eligible. Patients underwent involved-site radiotherapy at a dose of 12 Gy in four fractions. The primary endpoint was the complete response rate 6 months after radiotherapy. All analyses were performed in the intention-to-treat population. This trial was registered with ClinicalTrials.gov, NCT05543070, with a four-month delay due to the COVID-19 pandemic; recruitment is complete and follow-up is ongoing.FINDINGSBetween May 8, 2022, and Nov 8, 2023, 71 patients (with 73 target sites) were enrolled (median age 55 years [IQR 48-65]; 29 [41%] male and 42 [59%] female; and all were Asian). With a median follow-up of 19 months (IQR 16-22), the 6-month complete response was 95% (95% CI 87-98; 69 of 73 sites). The most common acute adverse events were grade 1 lymphopenia (20 [28%] of 71 patients) and grade 1 nausea (14 [19%] of 73 sites). The sole grade 3 or higher adverse event was grade 3 lymphopenia (eight [11%] of 71 patients). No treatment-related deaths were noted.INTERPRETATIONThe regimen of 12 Gy in four fractions is safe and shows promising activity as a local treatment for patients with indolent non-Hodgkin lymphoma. Given the retrospective registration of the trial, further studies evaluating the efficacy of this strategy are warranted.FUNDINGThe Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National High Level Hospital Clinical Research Funding, and the Beijing Hope Run Special Fund of Cancer Foundation of China.
背景：惰性非霍奇金淋巴瘤的放射治疗已经发展到优化最终剂量，同时最小化毒性。我们的目的是评估12 Gy低剂量放疗方案在惰性非霍奇金淋巴瘤患者中的活性和安全性。方法：这项多中心、单臂、2期试验研究纳入了来自中国4家医院的患者。新诊断或复发的I-IV期惰性非霍奇金淋巴瘤（滤泡性淋巴瘤、边缘区淋巴瘤和低级别淋巴瘤），年龄在18岁或以上，东部肿瘤合作组表现状态为0-3的患者符合条件。患者接受受累部位放疗，剂量为12 Gy，分为四部分。主要终点是放疗后6个月的完全缓解率。所有分析均在意向治疗人群中进行。该试验已在ClinicalTrials.gov注册，注册号为NCT05543070，由于COVID-19大流行而延迟了4个月；招聘已完成，后续工作正在进行中。结果：在2022年5月8日至2023年11月8日期间，纳入71例患者（73个靶点）(中位年龄55岁[IQR 48-65]；男性29人[41%]，女性42人[59%]；而且都是亚洲人)。中位随访19个月（IQR 16-22）， 6个月完全缓解率为95% (95% CI 87-98；73个地点中的69个)。最常见的急性不良事件是1级淋巴细胞减少（71例患者中有20例[28%]）和1级恶心（73例患者中有14例[19%]）。唯一的3级或以上不良事件是3级淋巴细胞减少（71例患者中有8例[11%]）。未发现与治疗相关的死亡。结论：12 Gy四组分的治疗方案是安全的，并且作为无痛性非霍奇金淋巴瘤患者的局部治疗显示出有希望的活性。鉴于该试验的回顾性注册，有必要进一步研究评估该策略的有效性。中国医学科学院医学科学创新基金、国家高水平医院临床研究基金、中国癌症基金会北京希望跑专项基金。
{"title":"Low-dose moderate hypofractionated radiotherapy for indolent non-Hodgkin lymphoma: a multicentre, single-arm, phase 2 trial.","authors":"Xin-Yue Wang,Xi-Mei Zhang,Liang Wang,Lin-Rui Gao,Ke Chen,Xiao-Li Feng,Wei Rao,Rong Zheng,Yun-Peng Wu,Yong-Wen Song,Hui Fang,Bo Chen,Jing Jin,Yue-Ping Liu,Hao Jing,Yuan Tang,Wen-Wen Zhang,Yi-Rui Zhai,Ning-Ning Lu,Ning Li,Chang-Fa Xia,Shu-Lian Wang,Xin Liu,Ye-Xiong Li,Shu-Nan Qi","doi":"10.1016/s2352-3026(25)00071-7","DOIUrl":"https://doi.org/10.1016/s2352-3026(25)00071-7","url":null,"abstract":"BACKGROUNDRadiotherapy for indolent non-Hodgkin lymphoma has evolved to optimise the definitive dose while minimising toxicity. We aimed to assess the activity and safety of a hypofractionated low-dose radiotherapy regimen of 12 Gy in four fractions in patients with indolent non-Hodgkin lymphoma.METHODSThis multicentre, single-arm, phase 2 trial study enrolled patients from four hospitals in China. Patients aged 18 years or older with newly diagnosed or relapsed stage I-IV indolent non-Hodgkin lymphoma (follicular lymphoma, marginal zone lymphoma, and low-grade lymphoma) and an Eastern Cooperative Oncology Group performance status of 0-3 were eligible. Patients underwent involved-site radiotherapy at a dose of 12 Gy in four fractions. The primary endpoint was the complete response rate 6 months after radiotherapy. All analyses were performed in the intention-to-treat population. This trial was registered with ClinicalTrials.gov, NCT05543070, with a four-month delay due to the COVID-19 pandemic; recruitment is complete and follow-up is ongoing.FINDINGSBetween May 8, 2022, and Nov 8, 2023, 71 patients (with 73 target sites) were enrolled (median age 55 years [IQR 48-65]; 29 [41%] male and 42 [59%] female; and all were Asian). With a median follow-up of 19 months (IQR 16-22), the 6-month complete response was 95% (95% CI 87-98; 69 of 73 sites). The most common acute adverse events were grade 1 lymphopenia (20 [28%] of 71 patients) and grade 1 nausea (14 [19%] of 73 sites). The sole grade 3 or higher adverse event was grade 3 lymphopenia (eight [11%] of 71 patients). No treatment-related deaths were noted.INTERPRETATIONThe regimen of 12 Gy in four fractions is safe and shows promising activity as a local treatment for patients with indolent non-Hodgkin lymphoma. Given the retrospective registration of the trial, further studies evaluating the efficacy of this strategy are warranted.FUNDINGThe Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National High Level Hospital Clinical Research Funding, and the Beijing Hope Run Special Fund of Cancer Foundation of China.","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914857","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 : 2025-05-01DOI: 10.1016/s2352-3026(25)00034-1
Michael Northend,William Wilson,Kushani Ediriwickrema,Laura Clifton-Hadley,Wendi Qian,Zaynab Rana,Tanya-Louise Martin,William Townsend,Moya Young,Fiona Miall,David Cunningham,Jan Walewski,Burhan Ferhanoglu,Kim Linton,Amanda Johnston,John F Seymour,David C Linch,Kirit M Ardeshna
BACKGROUNDInitial results of this study, reported after a median follow-up close to 4 years, demonstrated improved time to initiation of new treatment (TTNT) for patients with advanced stage, asymptomatic, low tumour burden follicular lymphoma who received early rituximab monotherapy when compared with watchful waiting. Given the long natural history of follicular lymphoma, the trial was extended to further assess TTNT with longer follow-up. Mature data are presented here.METHODSIn this open-label, randomised, phase 3 trial, conducted at 118 centres in five countries, adult patients with asymptomatic, stage II-IV, grade 1-3a low tumour burden follicular lymphoma and Eastern Cooperative Oncology Group performance status 0-1 were randomly assigned (1:1:1) between watchful waiting, rituximab induction (375 mg/m2, intravenous) weekly for four doses (rituximab induction group) and rituximab induction followed by rituximab maintenance at the same dose every 8 weeks for 12 doses (rituximab maintenance group). The rituximab induction group closed early on Sept 30, 2007, and the study was amended to a two-arm trial. The primary endpoint was TTNT, assessed in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT00112931, and recruitment and follow-up are complete.FINDINGSBetween Oct 15, 2004, and May 1, 2009, 455 patients were randomly assigned, including 183 to watchful waiting, 82 to rituximab induction, and 190 to rituximab maintenance. Median follow-up was 14·7 years (IQR 13·3-15·6). At 15 years, 65% (95% CI 56-72) of patients in the rituximab maintenance group, 48% (36-60) in the rituximab induction group, and 34% (27-42) in the watchful waiting group had not started new treatment. Median TTNT was not yet reached (95% CI 15·6-not estimable) in the rituximab maintenance group, 14·8 years (7·5-not reached) in the rituximab induction group, and 5·6 years (3·8-8·4) in the watchful waiting group. TTNT was longer in both the rituximab induction and rituximab maintenance groups compared with the watchful waiting group (rituximab induction vs watchful waiting: hazard ratio [HR] 0·55 [95% CI 0·38-0·80], p=0·0019; rituximab maintenance vs watchful waiting: HR 0·36 [0·26-0·50], p<0·0001).INTERPRETATIONThese mature data with 15 years of follow-up confirm that early rituximab monotherapy substantially delays the need for new treatment for patients with advanced stage, asymptomatic low tumour burden follicular lymphoma, providing an evidence base for its use in this setting and confirming its value for patients who seek to defer or avoid treatment with chemotherapy.FUNDINGCancer Research UK, Lymphoma Research Trust, Lymphoma Association, and Roche.
{"title":"Early rituximab monotherapy versus watchful waiting for advanced stage, asymptomatic, low tumour burden follicular lymphoma: long-term results of a randomised, phase 3 trial.","authors":"Michael Northend,William Wilson,Kushani Ediriwickrema,Laura Clifton-Hadley,Wendi Qian,Zaynab Rana,Tanya-Louise Martin,William Townsend,Moya Young,Fiona Miall,David Cunningham,Jan Walewski,Burhan Ferhanoglu,Kim Linton,Amanda Johnston,John F Seymour,David C Linch,Kirit M Ardeshna","doi":"10.1016/s2352-3026(25)00034-1","DOIUrl":"https://doi.org/10.1016/s2352-3026(25)00034-1","url":null,"abstract":"BACKGROUNDInitial results of this study, reported after a median follow-up close to 4 years, demonstrated improved time to initiation of new treatment (TTNT) for patients with advanced stage, asymptomatic, low tumour burden follicular lymphoma who received early rituximab monotherapy when compared with watchful waiting. Given the long natural history of follicular lymphoma, the trial was extended to further assess TTNT with longer follow-up. Mature data are presented here.METHODSIn this open-label, randomised, phase 3 trial, conducted at 118 centres in five countries, adult patients with asymptomatic, stage II-IV, grade 1-3a low tumour burden follicular lymphoma and Eastern Cooperative Oncology Group performance status 0-1 were randomly assigned (1:1:1) between watchful waiting, rituximab induction (375 mg/m2, intravenous) weekly for four doses (rituximab induction group) and rituximab induction followed by rituximab maintenance at the same dose every 8 weeks for 12 doses (rituximab maintenance group). The rituximab induction group closed early on Sept 30, 2007, and the study was amended to a two-arm trial. The primary endpoint was TTNT, assessed in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT00112931, and recruitment and follow-up are complete.FINDINGSBetween Oct 15, 2004, and May 1, 2009, 455 patients were randomly assigned, including 183 to watchful waiting, 82 to rituximab induction, and 190 to rituximab maintenance. Median follow-up was 14·7 years (IQR 13·3-15·6). At 15 years, 65% (95% CI 56-72) of patients in the rituximab maintenance group, 48% (36-60) in the rituximab induction group, and 34% (27-42) in the watchful waiting group had not started new treatment. Median TTNT was not yet reached (95% CI 15·6-not estimable) in the rituximab maintenance group, 14·8 years (7·5-not reached) in the rituximab induction group, and 5·6 years (3·8-8·4) in the watchful waiting group. TTNT was longer in both the rituximab induction and rituximab maintenance groups compared with the watchful waiting group (rituximab induction vs watchful waiting: hazard ratio [HR] 0·55 [95% CI 0·38-0·80], p=0·0019; rituximab maintenance vs watchful waiting: HR 0·36 [0·26-0·50], p<0·0001).INTERPRETATIONThese mature data with 15 years of follow-up confirm that early rituximab monotherapy substantially delays the need for new treatment for patients with advanced stage, asymptomatic low tumour burden follicular lymphoma, providing an evidence base for its use in this setting and confirming its value for patients who seek to defer or avoid treatment with chemotherapy.FUNDINGCancer Research UK, Lymphoma Research Trust, Lymphoma Association, and Roche.","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"2 1","pages":"e335-e345"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897469","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 : 2025-05-01DOI: 10.1016/s2352-3026(25)00105-x
Eva Kimby
{"title":"Rituximab versus active surveillance in patients with follicular lymphoma.","authors":"Eva Kimby","doi":"10.1016/s2352-3026(25)00105-x","DOIUrl":"https://doi.org/10.1016/s2352-3026(25)00105-x","url":null,"abstract":"","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"114 1","pages":"e320-e321"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897429","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 : 2025-05-01DOI: 10.1016/s2352-3026(25)00038-9
Ashley E Benson,Jamie O Lo,Maureen O Achebe,Jorgeane S Aslan,Michael Auerbach,Bethany T Samuelson Bannow,Marie J Boller,Thomas G Deloughery,Jacquelin Dingman,Layla Van Doren,Geolani W Dy,Patricia A Ford,Jason A Freed,Michael K Georgieff,Kristina M Haley,Chloe I Han,Adam K Lewkowitz,Kylee L Martens,Robert T Means,Elizabeta Nemeth,Sven R Olson,Jacquelyn M Powers,Kristin C Prewitt,Toby Richards,Don C Rockey,Eric J Roeland,Kimberly S Ryan,Hanny Al-Samkari,Michelle Sholzberg,Methodius G Tuuli,Angela C Weyand,Michelle P Zeller,Annette M Totten,Ilya Ivlev,Joseph J Shatzel,
Iron deficiency is the most common micronutrient deficiency worldwide. Oral iron is often recommended as first-line treatment, but there is no consensus on the optimal formulation, dosing strategy, or which patients should be treated preferentially with intravenous iron. To address these challenges, the Iron Consortium at Oregon Health & Science University (OHSU) convened an international panel of 26 experts in haematology, primary care, paediatrics, obstetrics, gastroenterology, cancer, and patient advocacy among its members. This panel was supplemented by insights from a four-person patient focus group to develop current recommendations using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The panel developed clinically relevant questions in five priority topic areas, a systematic literature search was performed, and studies meeting a priori criteria were included to generate evidence tables for recommendation development. Evidence-based and expert opinion-based recommendations were made through a structured anonymous consensus voting process at an in-person meeting in Portland, OR, USA, hosted by OHSU on Feb 16-17, 2024. The expert panel made seven evidence-based recommendations for three demographic groups with iron deficiency: non-pregnant adults, pregnant individuals, and infants, children, and adolescents. Expert opinions supported the recommendations on 21 aspects of care for which there is insufficient evidence. This Review provides evidence-based recommendations and expert consensus on the diagnosis, treatment, and management of iron deficiency, detailing best practices for oral and intravenous iron repletion across diverse patient populations.
{"title":"Management of iron deficiency in children, adults, and pregnant individuals: evidence-based and expert consensus recommendations.","authors":"Ashley E Benson,Jamie O Lo,Maureen O Achebe,Jorgeane S Aslan,Michael Auerbach,Bethany T Samuelson Bannow,Marie J Boller,Thomas G Deloughery,Jacquelin Dingman,Layla Van Doren,Geolani W Dy,Patricia A Ford,Jason A Freed,Michael K Georgieff,Kristina M Haley,Chloe I Han,Adam K Lewkowitz,Kylee L Martens,Robert T Means,Elizabeta Nemeth,Sven R Olson,Jacquelyn M Powers,Kristin C Prewitt,Toby Richards,Don C Rockey,Eric J Roeland,Kimberly S Ryan,Hanny Al-Samkari,Michelle Sholzberg,Methodius G Tuuli,Angela C Weyand,Michelle P Zeller,Annette M Totten,Ilya Ivlev,Joseph J Shatzel,","doi":"10.1016/s2352-3026(25)00038-9","DOIUrl":"https://doi.org/10.1016/s2352-3026(25)00038-9","url":null,"abstract":"Iron deficiency is the most common micronutrient deficiency worldwide. Oral iron is often recommended as first-line treatment, but there is no consensus on the optimal formulation, dosing strategy, or which patients should be treated preferentially with intravenous iron. To address these challenges, the Iron Consortium at Oregon Health & Science University (OHSU) convened an international panel of 26 experts in haematology, primary care, paediatrics, obstetrics, gastroenterology, cancer, and patient advocacy among its members. This panel was supplemented by insights from a four-person patient focus group to develop current recommendations using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The panel developed clinically relevant questions in five priority topic areas, a systematic literature search was performed, and studies meeting a priori criteria were included to generate evidence tables for recommendation development. Evidence-based and expert opinion-based recommendations were made through a structured anonymous consensus voting process at an in-person meeting in Portland, OR, USA, hosted by OHSU on Feb 16-17, 2024. The expert panel made seven evidence-based recommendations for three demographic groups with iron deficiency: non-pregnant adults, pregnant individuals, and infants, children, and adolescents. Expert opinions supported the recommendations on 21 aspects of care for which there is insufficient evidence. This Review provides evidence-based recommendations and expert consensus on the diagnosis, treatment, and management of iron deficiency, detailing best practices for oral and intravenous iron repletion across diverse patient populations.","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"13 1","pages":"e376-e388"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897467","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}
BACKGROUNDIn patients with acute myeloid leukaemia treated with curative intent, the detection of measurable residual disease (MRD) generally confers a poor prognosis. This study aimed to identify whether altering treatment based on MRD results can improve survival.METHODSIn the UK NCRI AML17 and AML19 randomised, controlled, phase 3 trials, performed in the UK, Denmark, and New Zealand, we screened patients aged 16-60 years with newly diagnosed acute myeloid leukaemia for molecular markers suitable for disease monitoring, including NPM1 mutations and fusion genes. Patients with a marker were randomly assigned (2:1) to either sequential molecular MRD monitoring during treatment and for 3 years after, or standard clinical care only with no molecular monitoring. In the monitoring group, treating physicians decided whether and how to incorporate the MRD results into the patient's therapy, including in cases of MRD relapse. The primary endpoint was overall survival. Prespecified subgroup analysis of the primary outcome included analysis by molecular group (NPM1mut with FLT3-ITD, NPM1mut without FLT3-ITD, and fusion gene transcripts). Both trials were registered with ISRCTN, ISRCTN55675535 and ISRCTN78449203, and are completed.FINDINGSIn the AML17 trial, 1836 patients were enrolled between June 1, 2012 and Dec 31, 2014. In the AML19 trial, 965 patients were enrolled between Nov 9, 2015, and Jan 23, 2018. 637 patients were randomly assigned across both trials (289 to MRD monitoring and 144 to no monitoring in AML17 and 136 to MRD monitoring and 68 to no monitoring in AML19). With a median follow-up time of 4·9 years (IQR 3·6-5·9), overall survival at 3 years was 70% (95% CI 66-75) in patients in the monitoring group and 73% (68-80) in patients in the no-monitoring group. Meta analysis of the two studies showed no difference in overall survival (hazard ratio [HR] 1·11, 95% CI 0·83-1·49; p=0·25). In the pre-specified subgroup analysis of the primary endpoint, overall survival at 3 years in patients with both NPM1 and FLT3 internal tandem duplication (ITD) mutations was 69% (95% CI 60-79) in the monitoring group and 58% (45-74) in the no-monitoring group (HR 0·53, 95% CI 0·31-0·91; p=0·021). However there was no difference in survival by randomisation in patients with NPM1 mutations without FLT3-ITD (overall survial 69% [95% CI 62-77] in the monitoring group and 78% [70-87] in the no monitoring group; HR 1·56, 95% CI 0·96-2·52) or those with fusion gene transcripts (overall survial 72% [95% CI 65-79] in the monitoring group and 77% [68-87] in the no monitoring group; HR 1·28, 95% CI 0·80-2·18).INTERPRETATIONSequential molecular MRD monitoring, coupled with MRD-guided treatment, did not improve overall survival in the entire study population; however, in the subgroup of patients with baseline NPM1 and FLT3 ITD mutations, we observed a survival benefit for MRD monitoring.FUNDINGNational Institute for Health Research, Blood Cancer UK, and Cancer Research UK.
背景：在以治愈为目的治疗的急性髓系白血病患者中，检测到可测量的残留疾病（MRD）通常会导致预后不良。本研究旨在确定基于MRD结果改变治疗是否可以提高生存率。方法在英国、丹麦和新西兰进行的英国NCRI AML17和AML19随机对照3期试验中，我们筛选了16-60岁新诊断的急性髓性白血病患者适合疾病监测的分子标记，包括NPM1突变和融合基因。具有标记物的患者被随机分配（2:1），在治疗期间和治疗后3年进行序列分子MRD监测，或仅进行标准临床治疗而不进行分子监测。在监测组，治疗医生决定是否以及如何将MRD结果纳入患者的治疗，包括在MRD复发的情况下。主要终点是总生存期。预先指定的主要结果亚组分析包括分子组分析（NPM1mut伴FLT3-ITD， NPM1mut不伴FLT3-ITD，以及融合基因转录物）。两项试验均已注册ISRCTN， ISRCTN55675535和ISRCTN78449203，并已完成。在AML17试验中，在2012年6月1日至2014年12月31日期间入组了1836名患者。在AML19试验中，在2015年11月9日至2018年1月23日期间招募了965名患者。637名患者被随机分配到两项试验中（AML17组289人进行MRD监测，144人不进行监测，AML19组136人进行MRD监测，68人不进行监测）。中位随访时间为4.9年（IQR为3.6 - 5.9），监测组患者3年总生存率为70% (95% CI 66-75)，无监测组患者3年总生存率为73%（68-80）。Meta分析显示两项研究的总生存率无差异(风险比[HR] 1.11, 95% CI 0.83 - 1.49；p = 0·25)。在预先指定的主要终点亚组分析中，同时存在NPM1和FLT3内部串联重复（ITD）突变的患者3年总生存率在监测组为69% (95% CI 60-79)，在无监测组为58% (45-74)(HR 0.53, 95% CI 0.31 - 0.91；p = 0·021)。然而，无FLT3-ITD的NPM1突变患者的随机化生存率没有差异(监测组的总生存率为69% [95% CI 62-77]，无监测组的总生存率为78% [70-87]；HR 1.56, 95% CI 0.96 - 2.52)或具有融合基因转录物的患者(总生存率监测组为72% [95% CI 65-79]，未监测组为77% [68-87]；Hr 1.28, 95% ci 0.80 - 2.18)。序列分子MRD监测，加上MRD引导治疗，并没有提高整个研究人群的总生存率；然而，在基线NPM1和FLT3 ITD突变的患者亚组中，我们观察到MRD监测的生存获益。英国国家健康研究所、英国血癌研究所和英国癌症研究所。
{"title":"Molecular monitoring versus standard clinical care in younger adults with acute myeloid leukaemia: results from the UK NCRI AML17 and AML19 randomised, controlled, phase 3 trials.","authors":"Nicola Potter,Jelena Jovanovic,Adam Ivey,Jad Othman,Abin Thomas,Amanda Gilkes,Manohursingh Runglall,Anju Kanda,Ian Thomas,Sean Johnson,Joanna Canham,William Villiers,Steven Knapper,Asim Khwaja,Mary Frances McMullin,Jamie Cavenagh,Ulrik Malthe Overgaard,Richard E Clark,Ellen Solomon,Sylvie D Freeman,Robert Hills,Alan Burnett,Nigel Russell,Richard Dillon,","doi":"10.1016/s2352-3026(25)00037-7","DOIUrl":"https://doi.org/10.1016/s2352-3026(25)00037-7","url":null,"abstract":"BACKGROUNDIn patients with acute myeloid leukaemia treated with curative intent, the detection of measurable residual disease (MRD) generally confers a poor prognosis. This study aimed to identify whether altering treatment based on MRD results can improve survival.METHODSIn the UK NCRI AML17 and AML19 randomised, controlled, phase 3 trials, performed in the UK, Denmark, and New Zealand, we screened patients aged 16-60 years with newly diagnosed acute myeloid leukaemia for molecular markers suitable for disease monitoring, including NPM1 mutations and fusion genes. Patients with a marker were randomly assigned (2:1) to either sequential molecular MRD monitoring during treatment and for 3 years after, or standard clinical care only with no molecular monitoring. In the monitoring group, treating physicians decided whether and how to incorporate the MRD results into the patient's therapy, including in cases of MRD relapse. The primary endpoint was overall survival. Prespecified subgroup analysis of the primary outcome included analysis by molecular group (NPM1mut with FLT3-ITD, NPM1mut without FLT3-ITD, and fusion gene transcripts). Both trials were registered with ISRCTN, ISRCTN55675535 and ISRCTN78449203, and are completed.FINDINGSIn the AML17 trial, 1836 patients were enrolled between June 1, 2012 and Dec 31, 2014. In the AML19 trial, 965 patients were enrolled between Nov 9, 2015, and Jan 23, 2018. 637 patients were randomly assigned across both trials (289 to MRD monitoring and 144 to no monitoring in AML17 and 136 to MRD monitoring and 68 to no monitoring in AML19). With a median follow-up time of 4·9 years (IQR 3·6-5·9), overall survival at 3 years was 70% (95% CI 66-75) in patients in the monitoring group and 73% (68-80) in patients in the no-monitoring group. Meta analysis of the two studies showed no difference in overall survival (hazard ratio [HR] 1·11, 95% CI 0·83-1·49; p=0·25). In the pre-specified subgroup analysis of the primary endpoint, overall survival at 3 years in patients with both NPM1 and FLT3 internal tandem duplication (ITD) mutations was 69% (95% CI 60-79) in the monitoring group and 58% (45-74) in the no-monitoring group (HR 0·53, 95% CI 0·31-0·91; p=0·021). However there was no difference in survival by randomisation in patients with NPM1 mutations without FLT3-ITD (overall survial 69% [95% CI 62-77] in the monitoring group and 78% [70-87] in the no monitoring group; HR 1·56, 95% CI 0·96-2·52) or those with fusion gene transcripts (overall survial 72% [95% CI 65-79] in the monitoring group and 77% [68-87] in the no monitoring group; HR 1·28, 95% CI 0·80-2·18).INTERPRETATIONSequential molecular MRD monitoring, coupled with MRD-guided treatment, did not improve overall survival in the entire study population; however, in the subgroup of patients with baseline NPM1 and FLT3 ITD mutations, we observed a survival benefit for MRD monitoring.FUNDINGNational Institute for Health Research, Blood Cancer UK, and Cancer Research UK.","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"48 1","pages":"e346-e356"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897466","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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