Pub Date : 2026-03-01Epub Date: 2026-01-30DOI: 10.1016/S2352-3026(25)00359-X
Fernando Barroso Duarte, Carmelo Gurnari, Donal P McLornan
The distinction between myelodysplastic syndromes and acute myeloid leukaemia remains a subject of debate, with direct implications for clinical decisions, trial eligibility, and allogeneic hematopoietic cell transplantation allocation. Although the historical 20% blast threshold in bone marrow is commonly used to separate myelodysplastic syndromes from acute myeloid leukaemia, emerging evidence shows that morphological, cytogenetic, and molecular features provide a more accurate framework for diagnosis and risk stratification. This Viewpoint discusses how advances in genomics and molecular biology have reshaped the classification of these disorders, highlighting molecular signatures and germline alterations as key tools to guide therapeutic decisions, transplant eligibility, and measurable residual disease assessment. We emphasise that myelodysplastic syndromes represent a biologically distinct entity to acute myeloid leukaemia, reinforcing the need to tailor treatment strategies according to disease biology to optimise patient outcomes.
{"title":"Myelodysplastic syndromes versus acute myeloid leukaemia: biology or blasts-what truly defines the disease and does it matter?","authors":"Fernando Barroso Duarte, Carmelo Gurnari, Donal P McLornan","doi":"10.1016/S2352-3026(25)00359-X","DOIUrl":"10.1016/S2352-3026(25)00359-X","url":null,"abstract":"<p><p>The distinction between myelodysplastic syndromes and acute myeloid leukaemia remains a subject of debate, with direct implications for clinical decisions, trial eligibility, and allogeneic hematopoietic cell transplantation allocation. Although the historical 20% blast threshold in bone marrow is commonly used to separate myelodysplastic syndromes from acute myeloid leukaemia, emerging evidence shows that morphological, cytogenetic, and molecular features provide a more accurate framework for diagnosis and risk stratification. This Viewpoint discusses how advances in genomics and molecular biology have reshaped the classification of these disorders, highlighting molecular signatures and germline alterations as key tools to guide therapeutic decisions, transplant eligibility, and measurable residual disease assessment. We emphasise that myelodysplastic syndromes represent a biologically distinct entity to acute myeloid leukaemia, reinforcing the need to tailor treatment strategies according to disease biology to optimise patient outcomes.</p>","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e181-e185"},"PeriodicalIF":17.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146107664","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 : 2026-03-01Epub Date: 2026-02-12DOI: 10.1016/S2352-3026(25)00357-6
Tanja A Gruber, Sima Jeha, Rebecca J Deyell, Victor Lewis, Bill H Chang, Eric J Lowe, Jamie Frediani, Catherine Vezina, Bruno Michon, Michael Richards, Erin H Breese, Thai-Hoa Tran, Norman Lacayo, Christine Bolen, Sunil Desai, Jennifer L Pauley, Minxuan Huang, Emily Ashcraft, Cheng Cheng, Kirk R Schultz, Linda Stork, Krysta Schlis, Van T Huynh, Nathan Gossai, Yoav H Messinger, Henrique Bittencourt, Terzah M Horton, Uma Athale, Duncan Stearns, Deborah Schiff, Paul S Gaynon
<p><strong>Background: </strong>Acute lymphoblastic leukaemia in infants remains a therapeutic challenge. In preclinical studies we previously identified bortezomib and vorinostat as active agents against KMT2A rearranged (KMT2Ar) leukaemia. The aim of this study was to determine the tolerability of incorporating bortezomib and vorinostat into an acute lymphoblastic leukaemia-chemotherapy backbone for newly diagnosed infants with acute lymphoblastic leukaemia both with and without KMT2Ar.</p><p><strong>Methods: </strong>In this single-arm phase 1/2 study conducted at 18 hospitals in the USA and Canada, we enrolled patients aged 1 year or younger at the time of diagnosis with newly diagnosed acute lymphoblastic leukaemia or undifferentiated leukaemia (with or without extramedullary disease) who had 25% or greater blasts in the bone marrow. Patients with T-cell acute lymphoblastic leukaemia were eligible, and patients with mixed-phenotype acute leukaemia were eligible provided the morphology and immunophenotype were predominantly lymphoid. We evaluated the incorporation of bortezomib (0·043 mg/kg intravenously once per day on days 1, 4, 8, 11, 15, and 18) and vorinostat into a chemotherapy backbone containing dexamethasone (5 mg/m<sup>2</sup> twice a day orally on days 1-4, 8-11, and 15-18), mitoxantrone (8 mg/m<sup>2</sup> intravenously once per day on days 8 and 9 during induction and days 1 and 2 during reinduction), and pegaspargase (2500 units/m<sup>2</sup> intravenously once per day on day 5 of induction and days 3 and 8 of reinduction) during the induction and reinduction cycles. Race and ethnicity data were parent reported. Gender was based on sex assigned at birth as determined by physical exam. A run-in dose escalation phase evaluated three doses of vorinostat (100, 150, and 180 mg/m<sup>2</sup> orally once per day on days 1-4, 8-11, and 15-18) followed by an expansion phase. The primary endpoint was completing induction and reinduction blocks with no protocol defined dose-limiting toxicities (DLT) in an intention-to-treat analysis. This trial is registered with ClinicalTrials.gov (NCT02553460) and this is the final report.</p><p><strong>Findings: </strong>From Jan 29, 2016, to Nov 17, 2021, 50 patients were enrolled to the study of whom 35 had KMT2Ar mutations. Median age was 171 days (IQR 100-276); patients were mostly White (31 [62%]), 26 (52%) patients were male and 24 (48%) were female. Median follow-up for alive patients was 4·9 years (IQR 3·6-6·0). No DLTs occurred in the first two vorinostat dose levels, and 44 patients received vorinostat at dose level 3 (DL3) in the dose expansion phase. Four patients treated at DL3 had protocol-defined induction DLTs and one patient treated at DL3 had a protocol defined reinduction DLT. The most frequently occurring grade 3-4 adverse events during induction (defined as occurring in 20% or more of participants) inclusive of all three dose levels included hypertension (24 [48%]), infection (22 [4
{"title":"Bortezomib and vorinostat in combination with mitoxantrone, dexamethasone, and pegasparaginase during induction and reinduction for infants with acute lymphoblastic leukaemia: a multicentre single-arm phase 1/2 study.","authors":"Tanja A Gruber, Sima Jeha, Rebecca J Deyell, Victor Lewis, Bill H Chang, Eric J Lowe, Jamie Frediani, Catherine Vezina, Bruno Michon, Michael Richards, Erin H Breese, Thai-Hoa Tran, Norman Lacayo, Christine Bolen, Sunil Desai, Jennifer L Pauley, Minxuan Huang, Emily Ashcraft, Cheng Cheng, Kirk R Schultz, Linda Stork, Krysta Schlis, Van T Huynh, Nathan Gossai, Yoav H Messinger, Henrique Bittencourt, Terzah M Horton, Uma Athale, Duncan Stearns, Deborah Schiff, Paul S Gaynon","doi":"10.1016/S2352-3026(25)00357-6","DOIUrl":"10.1016/S2352-3026(25)00357-6","url":null,"abstract":"<p><strong>Background: </strong>Acute lymphoblastic leukaemia in infants remains a therapeutic challenge. In preclinical studies we previously identified bortezomib and vorinostat as active agents against KMT2A rearranged (KMT2Ar) leukaemia. The aim of this study was to determine the tolerability of incorporating bortezomib and vorinostat into an acute lymphoblastic leukaemia-chemotherapy backbone for newly diagnosed infants with acute lymphoblastic leukaemia both with and without KMT2Ar.</p><p><strong>Methods: </strong>In this single-arm phase 1/2 study conducted at 18 hospitals in the USA and Canada, we enrolled patients aged 1 year or younger at the time of diagnosis with newly diagnosed acute lymphoblastic leukaemia or undifferentiated leukaemia (with or without extramedullary disease) who had 25% or greater blasts in the bone marrow. Patients with T-cell acute lymphoblastic leukaemia were eligible, and patients with mixed-phenotype acute leukaemia were eligible provided the morphology and immunophenotype were predominantly lymphoid. We evaluated the incorporation of bortezomib (0·043 mg/kg intravenously once per day on days 1, 4, 8, 11, 15, and 18) and vorinostat into a chemotherapy backbone containing dexamethasone (5 mg/m<sup>2</sup> twice a day orally on days 1-4, 8-11, and 15-18), mitoxantrone (8 mg/m<sup>2</sup> intravenously once per day on days 8 and 9 during induction and days 1 and 2 during reinduction), and pegaspargase (2500 units/m<sup>2</sup> intravenously once per day on day 5 of induction and days 3 and 8 of reinduction) during the induction and reinduction cycles. Race and ethnicity data were parent reported. Gender was based on sex assigned at birth as determined by physical exam. A run-in dose escalation phase evaluated three doses of vorinostat (100, 150, and 180 mg/m<sup>2</sup> orally once per day on days 1-4, 8-11, and 15-18) followed by an expansion phase. The primary endpoint was completing induction and reinduction blocks with no protocol defined dose-limiting toxicities (DLT) in an intention-to-treat analysis. This trial is registered with ClinicalTrials.gov (NCT02553460) and this is the final report.</p><p><strong>Findings: </strong>From Jan 29, 2016, to Nov 17, 2021, 50 patients were enrolled to the study of whom 35 had KMT2Ar mutations. Median age was 171 days (IQR 100-276); patients were mostly White (31 [62%]), 26 (52%) patients were male and 24 (48%) were female. Median follow-up for alive patients was 4·9 years (IQR 3·6-6·0). No DLTs occurred in the first two vorinostat dose levels, and 44 patients received vorinostat at dose level 3 (DL3) in the dose expansion phase. Four patients treated at DL3 had protocol-defined induction DLTs and one patient treated at DL3 had a protocol defined reinduction DLT. The most frequently occurring grade 3-4 adverse events during induction (defined as occurring in 20% or more of participants) inclusive of all three dose levels included hypertension (24 [48%]), infection (22 [4","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e144-e156"},"PeriodicalIF":17.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12998465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146203424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01DOI: 10.1016/S2352-3026(26)00010-4
Faizan Khan, Nick van Es
{"title":"Predictors of clinically relevant bleeding during extended anticoagulation for cancer-associated VTE.","authors":"Faizan Khan, Nick van Es","doi":"10.1016/S2352-3026(26)00010-4","DOIUrl":"https://doi.org/10.1016/S2352-3026(26)00010-4","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"13 3","pages":"e124-e125"},"PeriodicalIF":17.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147370509","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 : 2026-03-01DOI: 10.1016/S2352-3026(26)00032-3
Ankur Jain
{"title":"FAIR(er) treatment of non-anaemic iron deficiency during pregnancy?","authors":"Ankur Jain","doi":"10.1016/S2352-3026(26)00032-3","DOIUrl":"https://doi.org/10.1016/S2352-3026(26)00032-3","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"13 3","pages":"e126-e127"},"PeriodicalIF":17.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147370567","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 : 2026-03-01Epub Date: 2026-02-03DOI: 10.1016/S2352-3026(25)00328-X
Valentín Ortiz-Maldonado, Núria Martínez-Cibrian, Leticia Alserawan, Marta Español-Rego, Sergio Navarro-Velázquez, Nil Albiol, Aina Oliver-Caldés, Ana Triguero, María Herrero-García, Sara Gutiérrez-Herrero, Daniel Benítez-Ribas, María Liz Paciello, Anna Torrent, Javier Delgado-Serrano, María Sánchez-Castañón, Hugo Calderón, Juan José Mata, Andrés Sánchez-Salinas, Joaquín Sáez-Peñataro, Carla Sans-Pola, Maria Calvo-Orteu, Lucía López-Corral, Mi Kwon, José Rifón, Paola Charry, Rafael Alberto Alonso-Fernández, María Huguet, Cristina Blázquez-Goñi, José María Sánchez-Pina, Ricardo Sánchez, Juan Manuel Rosa-Rosa, Joaquín Martínez-López, Miguel Blanquer, Josep Maria Ribera, Álvaro Urbano-Ispizua, Mireia Bachiller, Laura Palau, Eulalia Olesti, Gonzalo Calvo, Lourdes Martín-Martín, Alberto Orfao, E Azucena González-Navarro, Gemma Domenech, Sara Varea, Manel Juan, Julio Delgado, Jordi Esteve
<p><strong>Background: </strong>Varnimcabtagene autoleucel (var-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy with adaptive intra-patient dose escalation and was approved in Spain in 2021 for patients older than 25 years with relapsed or refractory B-cell precursor acute lymphoblastic leukaemia. We report activity and safety from var-cel's pivotal trial in this patient population.</p><p><strong>Methods: </strong>This multicentre, single-arm, phase 2 trial was conducted at nine academic centres in Spain. Eligible patients had CD19<sup>+</sup> B-cell precursor acute lymphoblastic leukaemia in the first relapse or refractory disease, either ineligible for allogeneic haematopoietic cell transplantation (HCT) or with relapsed disease after allogeneic HCT; centralised measurable disease in peripheral blood or bone marrow, or both, using flow cytometry; were aged 18-70 years; and had an Eastern Cooperative Oncology Group performance status of 0-2. Patients received a single course of intravenous lymphodepleting chemotherapy with fludarabine (30 mg/m<sup>2</sup> per day for 3 days) plus cyclophosphamide (300 mg/m<sup>2</sup> per day for 3 days), followed by intravenous fractionated var-cel escalation (0·1, 0·3, 0·6, and 2·0 × 10<sup>6</sup> CAR T cells per kg) separated by at least 24 h, with each fraction contingent on safety criteria. The primary endpoint was complete response with undetected measurable residual disease (MRD; sensitivity of ≤10<sup>-5</sup>) determined by flow cytometry by day 28 from var-cel administration, assessed in the efficacy population (defined as all patients who received at least one var-cel fraction). Safety was analysed in patients that initiated lymphodepletion. This study is registered with ClinicalTrials.gov, NCT04778579 (completed).</p><p><strong>Findings: </strong>Between May 19, 2021, and July 6, 2023, 50 patients were assessed for eligibility, 12 were ineligible, and 38 were enrolled. 37 (97%) of 38 underwent leukapheresis (ITT population), 33 (87%) initiated lymphodepleting chemotherapy (safety population), and 32 (84%) received at least one var-cel fraction (efficacy population). Five patients who underwent leukapheresis did not receive var-cel due to rapid disease progression (n=3), death due to veno-oclusive disease (n=1), and persistent COVID-19 (n=1). Patients receiving var-cel had a median age of 40 years (33-48); of whom, 16 (50%) were female and 16 (50%) were male. By data cutoff (Jan 18, 2024), the median follow-up from infusion was 8·6 months (IQR 5·1-14·4) and 27 (84·4% [95% CI 67·2-94·7]) of 32 patients who received at least one dose of var-cel had a complete response with undetected MRD by day 28. Treatment-emergent adverse events occurred in 31 (94%) of 33 patients. The most common grade 3 or higher adverse events were neutropenia in 15 (45%) patients, thrombocytopenia in seven (21%), anaemia in five (15%), and cytokine release syndrome in four (12%). Immune effecto
{"title":"Varnimcabtagene autoleucel for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukaemia in Spain (CART19-BE-02): a multicentre, single-arm, phase 2 trial.","authors":"Valentín Ortiz-Maldonado, Núria Martínez-Cibrian, Leticia Alserawan, Marta Español-Rego, Sergio Navarro-Velázquez, Nil Albiol, Aina Oliver-Caldés, Ana Triguero, María Herrero-García, Sara Gutiérrez-Herrero, Daniel Benítez-Ribas, María Liz Paciello, Anna Torrent, Javier Delgado-Serrano, María Sánchez-Castañón, Hugo Calderón, Juan José Mata, Andrés Sánchez-Salinas, Joaquín Sáez-Peñataro, Carla Sans-Pola, Maria Calvo-Orteu, Lucía López-Corral, Mi Kwon, José Rifón, Paola Charry, Rafael Alberto Alonso-Fernández, María Huguet, Cristina Blázquez-Goñi, José María Sánchez-Pina, Ricardo Sánchez, Juan Manuel Rosa-Rosa, Joaquín Martínez-López, Miguel Blanquer, Josep Maria Ribera, Álvaro Urbano-Ispizua, Mireia Bachiller, Laura Palau, Eulalia Olesti, Gonzalo Calvo, Lourdes Martín-Martín, Alberto Orfao, E Azucena González-Navarro, Gemma Domenech, Sara Varea, Manel Juan, Julio Delgado, Jordi Esteve","doi":"10.1016/S2352-3026(25)00328-X","DOIUrl":"10.1016/S2352-3026(25)00328-X","url":null,"abstract":"<p><strong>Background: </strong>Varnimcabtagene autoleucel (var-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy with adaptive intra-patient dose escalation and was approved in Spain in 2021 for patients older than 25 years with relapsed or refractory B-cell precursor acute lymphoblastic leukaemia. We report activity and safety from var-cel's pivotal trial in this patient population.</p><p><strong>Methods: </strong>This multicentre, single-arm, phase 2 trial was conducted at nine academic centres in Spain. Eligible patients had CD19<sup>+</sup> B-cell precursor acute lymphoblastic leukaemia in the first relapse or refractory disease, either ineligible for allogeneic haematopoietic cell transplantation (HCT) or with relapsed disease after allogeneic HCT; centralised measurable disease in peripheral blood or bone marrow, or both, using flow cytometry; were aged 18-70 years; and had an Eastern Cooperative Oncology Group performance status of 0-2. Patients received a single course of intravenous lymphodepleting chemotherapy with fludarabine (30 mg/m<sup>2</sup> per day for 3 days) plus cyclophosphamide (300 mg/m<sup>2</sup> per day for 3 days), followed by intravenous fractionated var-cel escalation (0·1, 0·3, 0·6, and 2·0 × 10<sup>6</sup> CAR T cells per kg) separated by at least 24 h, with each fraction contingent on safety criteria. The primary endpoint was complete response with undetected measurable residual disease (MRD; sensitivity of ≤10<sup>-5</sup>) determined by flow cytometry by day 28 from var-cel administration, assessed in the efficacy population (defined as all patients who received at least one var-cel fraction). Safety was analysed in patients that initiated lymphodepletion. This study is registered with ClinicalTrials.gov, NCT04778579 (completed).</p><p><strong>Findings: </strong>Between May 19, 2021, and July 6, 2023, 50 patients were assessed for eligibility, 12 were ineligible, and 38 were enrolled. 37 (97%) of 38 underwent leukapheresis (ITT population), 33 (87%) initiated lymphodepleting chemotherapy (safety population), and 32 (84%) received at least one var-cel fraction (efficacy population). Five patients who underwent leukapheresis did not receive var-cel due to rapid disease progression (n=3), death due to veno-oclusive disease (n=1), and persistent COVID-19 (n=1). Patients receiving var-cel had a median age of 40 years (33-48); of whom, 16 (50%) were female and 16 (50%) were male. By data cutoff (Jan 18, 2024), the median follow-up from infusion was 8·6 months (IQR 5·1-14·4) and 27 (84·4% [95% CI 67·2-94·7]) of 32 patients who received at least one dose of var-cel had a complete response with undetected MRD by day 28. Treatment-emergent adverse events occurred in 31 (94%) of 33 patients. The most common grade 3 or higher adverse events were neutropenia in 15 (45%) patients, thrombocytopenia in seven (21%), anaemia in five (15%), and cytokine release syndrome in four (12%). Immune effecto","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e133-e143"},"PeriodicalIF":17.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146133426","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 : 2026-02-01DOI: 10.1016/S2352-3026(25)00322-9
Rudolf Stadler, Pietro Quaglino, F J Sherida H Woei-A-Jin, Reinhard Dummer, Christina Mitteldorf, Evangelia Papadavid, Pablo L Ortiz Romero, Emmanuella Guenova, Riichiro Abe, Richard Cowan, Martine Bagot, Stéphane Dalle, Taku Fujimura, Thilo Gambichler, Stephen Morris, Ulrike Wehkamp, Patrick Terheyden, Antonio Cozzio, Edgar Dippel, Silvia Alberti-Violetti, Joanna Romejko-Jarosinska, Anna Wozniacka, Eva González Barca, Ramon Pujol Vallverdu, Egle Ramelyte, Oliver Bechter, Kenta Suzuki, Robert Knobler, Susanne Danhauser-Riedl, Julia Scarisbrick
<p><strong>Background: </strong>In advanced-stage cutaneous T-cell lymphoma (CTCL), current therapeutic options rarely provide long-lasting responses. We aimed to evaluate the efficacy and safety of a histone deacetylase inhibitor, resminostat, as maintenance therapy in patients with advanced-stage mycosis fungoides or Sézary syndrome, in whom disease control had been previously met.</p><p><strong>Methods: </strong>We conducted a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial (RESMAIN) at 55 medical centres in Austria, Belgium, France, Germany, Greece, Italy, the Netherlands, Poland, Spain, Switzerland, the UK, and Japan. Adult patients (aged ≥18 years) with histologically confirmed, stage IIB-IVB mycosis fungoides or Sézary syndrome; an Eastern Cooperative Oncology Group performance status score of 0-2; and disease control after at least one previous systemic therapy or total skin electron beam were eligible for inclusion. Patients were randomly assigned to receive either oral resminostat (600 mg) or matching oral placebo once daily for 5 days, followed by a treatment-free period of 9 days, within a 14-day treatment cycle. Randomisation was stratified by disease stage (IIB-IVA1 vs IVA2-IVB) and remission status following previous therapy (complete or partial response vs stable disease) by use of a dynamic block allocation process (block size 100 patients). Participants, investigators, site staff, and study personnel involved in outcome assessment and data analysis were masked to group assignment. Patients with disease progression during masked treatment were unmasked; patients on placebo were offered open-label resminostat. Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, defined as the time from randomisation to disease progression or death from any cause (whichever occurred first), analysed by intention to treat. This trial is registered with ClincalTrials.gov (NCT02953301) and has been completed.</p><p><strong>Findings: </strong>Between Jan 9, 2017, and May 11, 2022, 234 patients were screened for eligibility, of whom 201 (86%) patients were randomly assigned: 100 (50%) to resminostat and 101 (50%) to placebo. 123 (61%) participants were men and 78 (39%) were women, with a median age of 64 years (range 30-87). Most participants (173 [86%]) were White, 19 (9%) were Asian (mainly Japanese), two (1%) were Black, and seven (3%) were either another race or ethnicity, or did not disclose these data. Median progression-free survival was 8·3 months (95% CI 4·2-15·7) in the resminostat group and 4·2 months (2·8-6·4) in the placebo group (HR 0·62 [95% CI 0·42-0·92]; p=0·015). Median follow-up time for progression-free survival was 11·2 months (95% CI 5·6-19·6) in the resminostat group and 17·0 months (13·9-30·5) in the placebo group. Adverse events were reported in 96 (96%) patients receiving resminostat and in 81 (80%) patients receiving placebo. S
背景：在晚期皮肤t细胞淋巴瘤（CTCL）中，目前的治疗方案很少能提供持久的疗效。我们的目的是评估组蛋白去乙酰化酶抑制剂resminostat作为晚期蕈样真菌病或ssamzary综合征患者维持治疗的有效性和安全性，这些患者先前已经达到疾病控制。方法：我们在奥地利、比利时、法国、德国、希腊、意大利、荷兰、波兰、西班牙、瑞士、英国和日本的55个医疗中心进行了一项多中心、双盲、随机、安慰剂对照的2期试验（RESMAIN）。组织学证实的IIB-IVB期蕈样真菌病或ssamzary综合征的成年患者（年龄≥18岁）；a东部肿瘤合作组绩效状态评分0-2分；在至少一次以前的全身治疗或全皮肤电子束治疗后的疾病控制符合纳入条件。患者被随机分配接受口服雷米诺他（600毫克）或相匹配的口服安慰剂，每天一次，持续5天，随后在14天的治疗周期内无治疗9天。随机化根据疾病分期（IIB-IVA1 vs IVA2-IVB）和既往治疗后的缓解状态（完全或部分缓解vs疾病稳定）进行分层，采用动态分组分配过程（分组大小为100例）。参与结果评估和数据分析的参与者、研究者、现场工作人员和研究人员被分组分配。在蒙面治疗期间疾病进展的患者被揭开蒙面；服用安慰剂的患者给予开放标签的雷米司他。治疗持续到疾病进展或不可接受的毒性。主要终点是无进展生存期，定义为从随机化到疾病进展或任何原因死亡（以先发生者为准）的时间，并通过治疗意向进行分析。该试验已在clinaltrials .gov注册（NCT02953301），并已完成。研究结果：在2017年1月9日至2022年5月11日期间，筛选了234名患者，其中201名（86%）患者被随机分配：100名（50%）患者接受雷米诺他治疗，101名（50%）患者接受安慰剂治疗。123名（61%）参与者为男性，78名（39%）参与者为女性，中位年龄为64岁（30-87岁）。大多数参与者（173人[86%]）是白人，19人（9%）是亚洲人（主要是日本人），2人（1%）是黑人，7人（3%）是其他种族或族裔，或没有透露这些数据。雷米诺他组的中位无进展生存期为8.3个月（95% CI 4.2 - 15.7），安慰剂组的中位无进展生存期为4.2个月（2.8 - 6.4）（HR 0.62 [95% CI 0.42 - 0.92]; p= 0.015）。雷米诺他组无进展生存期的中位随访时间为11.2个月（95% CI为5.6 - 19.6），安慰剂组为17.0个月（13.9 - 30.5）。96例（96%）接受雷米司他治疗的患者报告了不良事件，81例（80%）接受安慰剂治疗的患者报告了不良事件。雷米司他组有19例（19%）患者发生严重不良事件，其中11例（11%）被认为与治疗有关，安慰剂组有12例（12%）患者发生严重不良事件，其中1例（1%）被认为与治疗有关。雷米诺他组38例（38%）患者发生3级或以上不良事件，安慰剂组15例（15%）患者发生3级或以上不良事件。最常见的治疗相关不良事件是恶心（雷米诺他组68例[68%]对安慰剂组6例[6%]）、腹泻（44例[44%]对9例[9%]）、呕吐（32例[32%]对1例[1%]）和疲劳（29例[29%]对14例[14%]）。没有与治疗相关的死亡。解释：这些发现支持雷米司他维持治疗对晚期CTCL患者的有益效果。瑞米司他的总体安全性是可以接受的，胃肠道副作用是最常见的。未来应考虑预防止吐，以控制副作用，提高耐受性和对维持治疗的依从性。资助：4SC AG。
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