Pub Date : 2025-08-01DOI: 10.1016/s2352-3026(25)00160-7
Areej El-Jawahri,Lara Traeger,Jennifer B Reese,Don Dizon,Sharon L Bober,Joseph A Greer,Julie Vanderklish,Nora Horick,Nneka Ufere,Mathew J Reynolds,Julia Rice,Madison Clay,Richard Newcomb,Zachariah DeFilipp,Yi-Bin Chen,Jennifer S Temel
BACKGROUNDSexual dysfunction is a common complication affecting survivors of haematopoietic stem-cell transplantation (HSCT). Interventions to address sexual health in survivors of HSCT are limited. We aimed to assess the efficacy of a multimodal sexual dysfunction intervention for improving sexual health, quality of life (QOL), and psychological outcomes in survivors of HSCT.METHODSWe conducted a single-centre, open-label, randomised clinical trial of a multimodal intervention to address sexual dysfunction in survivors of HSCT at Massachusetts General Hospital. Participants were aged 18 years or older, had a haematological malignancy, and had undergone autologous or allogeneic HSCT at least 3 months before study enrolment, with a positive screening for sexual dysfunction causing distress according to the National Comprehensive Cancer Network survival guidelines. Patients were randomly assigned to the intervention (participants met with a trained HSCT clinician for an initial 60 mins visit, followed by two 30-45 mins monthly visits, either in person, by telephone, or over a secure video platform) or enhanced usual care (EUC) using computer-generated block randomisation, stratified by transplantation type and sex. The primary endpoint was to compare global satisfaction with sex scores (PROMIS sexual function and satisfaction measure) at 3 months between the study groups. We conducted analyses in accordance with the intention-to-treat principle. This study was registered with ClinicalTrials.gov (NCT03803696) and is complete.FINDINGSBetween Feb 15, 2019 and Feb 3, 2023, 125 (74%) of 169 eligible patients were enrolled to the study. Enrolled patients were mostly White (107 [86%] of 125), non-Hispanic (113 [90%]), and male (84 [67%]), and had a median age of 57·8 years (IQR 46·5-65·8, range 20·3-81·9). 91 (73%) had received an allogeneic HSCT. At 3 months, patients randomised to the intervention reported better global satisfaction with sex (11·5 [SD 5·1] at baseline to 15·8 [SD 5·3] at 3 months) compared to EUC (from 11·1 [4·5] to 11·2 [SD 5·1]; mean difference 4·7 [95% CI 3·0-6·3], Cohen's d=0·85, p<0·0001).INTERPRETATIONA multimodal intervention delivered by trained HSCT clinicians resulted in improvements in global satisfaction with sex. These findings underscore the potential of this intervention to be integrated into routine transplant care to improve sexual health outcomes for HSCT survivors.FUNDINGAmerican Cancer Society and the Leukemia & Lymphoma Society.
{"title":"A multimodal sexual dysfunction intervention versus enhanced usual care for survivors of haematopoietic stem-cell transplantation: a single-centre, open-label, randomised clinical trial.","authors":"Areej El-Jawahri,Lara Traeger,Jennifer B Reese,Don Dizon,Sharon L Bober,Joseph A Greer,Julie Vanderklish,Nora Horick,Nneka Ufere,Mathew J Reynolds,Julia Rice,Madison Clay,Richard Newcomb,Zachariah DeFilipp,Yi-Bin Chen,Jennifer S Temel","doi":"10.1016/s2352-3026(25)00160-7","DOIUrl":"https://doi.org/10.1016/s2352-3026(25)00160-7","url":null,"abstract":"BACKGROUNDSexual dysfunction is a common complication affecting survivors of haematopoietic stem-cell transplantation (HSCT). Interventions to address sexual health in survivors of HSCT are limited. We aimed to assess the efficacy of a multimodal sexual dysfunction intervention for improving sexual health, quality of life (QOL), and psychological outcomes in survivors of HSCT.METHODSWe conducted a single-centre, open-label, randomised clinical trial of a multimodal intervention to address sexual dysfunction in survivors of HSCT at Massachusetts General Hospital. Participants were aged 18 years or older, had a haematological malignancy, and had undergone autologous or allogeneic HSCT at least 3 months before study enrolment, with a positive screening for sexual dysfunction causing distress according to the National Comprehensive Cancer Network survival guidelines. Patients were randomly assigned to the intervention (participants met with a trained HSCT clinician for an initial 60 mins visit, followed by two 30-45 mins monthly visits, either in person, by telephone, or over a secure video platform) or enhanced usual care (EUC) using computer-generated block randomisation, stratified by transplantation type and sex. The primary endpoint was to compare global satisfaction with sex scores (PROMIS sexual function and satisfaction measure) at 3 months between the study groups. We conducted analyses in accordance with the intention-to-treat principle. This study was registered with ClinicalTrials.gov (NCT03803696) and is complete.FINDINGSBetween Feb 15, 2019 and Feb 3, 2023, 125 (74%) of 169 eligible patients were enrolled to the study. Enrolled patients were mostly White (107 [86%] of 125), non-Hispanic (113 [90%]), and male (84 [67%]), and had a median age of 57·8 years (IQR 46·5-65·8, range 20·3-81·9). 91 (73%) had received an allogeneic HSCT. At 3 months, patients randomised to the intervention reported better global satisfaction with sex (11·5 [SD 5·1] at baseline to 15·8 [SD 5·3] at 3 months) compared to EUC (from 11·1 [4·5] to 11·2 [SD 5·1]; mean difference 4·7 [95% CI 3·0-6·3], Cohen's d=0·85, p<0·0001).INTERPRETATIONA multimodal intervention delivered by trained HSCT clinicians resulted in improvements in global satisfaction with sex. These findings underscore the potential of this intervention to be integrated into routine transplant care to improve sexual health outcomes for HSCT survivors.FUNDINGAmerican Cancer Society and the Leukemia & Lymphoma Society.","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"1 1","pages":"e611-e620"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144791934","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 : 2025-08-01DOI: 10.1016/s2352-3026(25)00143-7
María-Victoria Mateos,Bruno Paiva,M Teresa Cedena,Noemí Puig,Ana Maria Sureda-Balari,Verónica Gonzalez de la Calle,Albert Oriol,Enrique M Ocio,Laura Rosiñol,Yolanda González Montes,Joan Bargay,María Esther González García,Sunil Lakhwani,Angel Ramirez Payer,Alexia Suarez-Cabrera,María-Jesús Blanchard,Sebastián Garzón,Felipe Casado Montero,Valentín Cabañas,Jaime Pérez de Oteyza,Mercedes Gironella,Joaquín Martinez-Lopez,Ana Isabel Teruel Casasús,María Pilar Delgado-Beltrán,Elena Prieto,Juan José Lahuerta,Joan Bladé,Jesús San-Miguel
BACKGROUNDTriplet and quadruplet regimens based on bortezomib, melphalan and prednisone (VMP) and lenalidomide and dexamethasone (Rd) with anti-CD38 antibodies are potential treatments for transplant-ineligible patients with newly diagnosed multiple myeloma. However, the high risk of toxic effects in this population requires frailty-based therapy adaptation. We aimed to compare the response of carfilzomib-based triplet and quadruplet regimens with a VMP-Rd regimen in newly diagnosed transplant-ineligible patients with multiple myeloma, considering patient frailty.METHODSGEM-2017FIT was an open-label, randomised, phase 3 trial at 57 hospitals in Spain. Patients aged 65-80 years were enrolled and assessed for frailty using the Geriatric Assessment in Hematology (GAH) scale. Patients were randomly assigned (1:1:1) to receive 18-cycle induction therapy of VMP 9-Rd 9 (one six-week cycle of melphalan 9 mg/m2 and prednisone 60 mg/m2 on days 1-4; bortezomib 1·3 mg/m2 subcutaneous twice weekly, followed by eight four-week cycles of weekly VMP and nine four-week cycles of lenalidomide 25 mg on days 1-21 and dexamethasone 40 mg weekly), carfilzomib-based triplet (KRd; carfilzomib intravenously 20 mg/m2 [only in the infusion on day 1 in first cycle] or 36 mg/m2 on days 1, 2, 8, 9, 15, and 16 in cycles 1-2, 56 mg/m2 in cycles 3-18, plus Rd) or daratumumab-KRd (D-KRd; daratumumab 16 mg/kg intravenous weekly [cycles 1-2], biweekly [cycles 3-6], and every 4 weeks [cycles 7-18]). All patients who completed induction therapy and consolidation were stratified by measurable residual disease status and both those with undetectable measurable residual disease and detectable measurable residual disease were subsequently randomly assigned (1:1) to maintenance therapy with daratumumab and lenalidomide or no maintenance therapy. The primary endpoint was measurable residual disease negativity after induction, which was assessed in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, NCT03742297.FINDINGSBetween October 15, 2018 and December 15, 2021, 540 patients were enrolled and assessed for eligibility. 462 were eligible for the study and randomly assigned to VMP 9-Rd 9 (n=154), KRd (n=154) or D-KRd (n=154, with one patient subsequently found to be ineligible). 230 (50%) of 461 patients were male and 231 (50%) were female. Patients were followed up for a median of 33·15 months (IQR 25·82-43·08). The 18-cycle undetectable measurable residual disease rate with a sensitivity level of 10-5 in the intention-to-treat population was higher in the KRd group (83 [54%] of 154 patients; odds ratio [OR] 1·73, 95% CI 1·39-2·16; p<0·0001) and D-KRd group (94 [61%] of 153 patients; 2·03, 1·61-2·57; p<0·0001) than in the VMP 9-Rd 9 group (41 [27%] of 154 patients). The incidence of grade 3-4 neutropenia was lower in the KRd group (37 [24%] of 154 patients) compared with the VMP 9-Rd 9 group (62 [40%] of 154 patients) and D-KRd group (63 [41%] of 153 patien
{"title":"Induction therapy with bortezomib, melphalan, and prednisone followed by lenalidomide and dexamethasone versus carfilzomib, lenalidomide, and dexamethasone with or without daratumumab in older, fit patients with newly diagnosed multiple myeloma (GEM-2017FIT): a phase 3, open-label, multicentre, randomised clinical trial.","authors":"María-Victoria Mateos,Bruno Paiva,M Teresa Cedena,Noemí Puig,Ana Maria Sureda-Balari,Verónica Gonzalez de la Calle,Albert Oriol,Enrique M Ocio,Laura Rosiñol,Yolanda González Montes,Joan Bargay,María Esther González García,Sunil Lakhwani,Angel Ramirez Payer,Alexia Suarez-Cabrera,María-Jesús Blanchard,Sebastián Garzón,Felipe Casado Montero,Valentín Cabañas,Jaime Pérez de Oteyza,Mercedes Gironella,Joaquín Martinez-Lopez,Ana Isabel Teruel Casasús,María Pilar Delgado-Beltrán,Elena Prieto,Juan José Lahuerta,Joan Bladé,Jesús San-Miguel","doi":"10.1016/s2352-3026(25)00143-7","DOIUrl":"https://doi.org/10.1016/s2352-3026(25)00143-7","url":null,"abstract":"BACKGROUNDTriplet and quadruplet regimens based on bortezomib, melphalan and prednisone (VMP) and lenalidomide and dexamethasone (Rd) with anti-CD38 antibodies are potential treatments for transplant-ineligible patients with newly diagnosed multiple myeloma. However, the high risk of toxic effects in this population requires frailty-based therapy adaptation. We aimed to compare the response of carfilzomib-based triplet and quadruplet regimens with a VMP-Rd regimen in newly diagnosed transplant-ineligible patients with multiple myeloma, considering patient frailty.METHODSGEM-2017FIT was an open-label, randomised, phase 3 trial at 57 hospitals in Spain. Patients aged 65-80 years were enrolled and assessed for frailty using the Geriatric Assessment in Hematology (GAH) scale. Patients were randomly assigned (1:1:1) to receive 18-cycle induction therapy of VMP 9-Rd 9 (one six-week cycle of melphalan 9 mg/m2 and prednisone 60 mg/m2 on days 1-4; bortezomib 1·3 mg/m2 subcutaneous twice weekly, followed by eight four-week cycles of weekly VMP and nine four-week cycles of lenalidomide 25 mg on days 1-21 and dexamethasone 40 mg weekly), carfilzomib-based triplet (KRd; carfilzomib intravenously 20 mg/m2 [only in the infusion on day 1 in first cycle] or 36 mg/m2 on days 1, 2, 8, 9, 15, and 16 in cycles 1-2, 56 mg/m2 in cycles 3-18, plus Rd) or daratumumab-KRd (D-KRd; daratumumab 16 mg/kg intravenous weekly [cycles 1-2], biweekly [cycles 3-6], and every 4 weeks [cycles 7-18]). All patients who completed induction therapy and consolidation were stratified by measurable residual disease status and both those with undetectable measurable residual disease and detectable measurable residual disease were subsequently randomly assigned (1:1) to maintenance therapy with daratumumab and lenalidomide or no maintenance therapy. The primary endpoint was measurable residual disease negativity after induction, which was assessed in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, NCT03742297.FINDINGSBetween October 15, 2018 and December 15, 2021, 540 patients were enrolled and assessed for eligibility. 462 were eligible for the study and randomly assigned to VMP 9-Rd 9 (n=154), KRd (n=154) or D-KRd (n=154, with one patient subsequently found to be ineligible). 230 (50%) of 461 patients were male and 231 (50%) were female. Patients were followed up for a median of 33·15 months (IQR 25·82-43·08). The 18-cycle undetectable measurable residual disease rate with a sensitivity level of 10-5 in the intention-to-treat population was higher in the KRd group (83 [54%] of 154 patients; odds ratio [OR] 1·73, 95% CI 1·39-2·16; p<0·0001) and D-KRd group (94 [61%] of 153 patients; 2·03, 1·61-2·57; p<0·0001) than in the VMP 9-Rd 9 group (41 [27%] of 154 patients). The incidence of grade 3-4 neutropenia was lower in the KRd group (37 [24%] of 154 patients) compared with the VMP 9-Rd 9 group (62 [40%] of 154 patients) and D-KRd group (63 [41%] of 153 patien","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"14 1","pages":"e588-e598"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144791933","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 : 2025-08-01DOI: 10.1016/s2352-3026(25)00202-9
Pamela Stratton
{"title":"Enhancing sexual function after haematopoietic transplantation.","authors":"Pamela Stratton","doi":"10.1016/s2352-3026(25)00202-9","DOIUrl":"https://doi.org/10.1016/s2352-3026(25)00202-9","url":null,"abstract":"","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"20 1","pages":"e562-e563"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144791834","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 : 2025-08-01DOI: 10.1016/s2352-3026(25)00140-1
Alanna Wood,Jason Daley,Duminda Perera,Anne Lee
{"title":"Intractable hyphaema following cataract surgery and microstent insertion in a patient on zanubrutinib.","authors":"Alanna Wood,Jason Daley,Duminda Perera,Anne Lee","doi":"10.1016/s2352-3026(25)00140-1","DOIUrl":"https://doi.org/10.1016/s2352-3026(25)00140-1","url":null,"abstract":"","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"78 1","pages":"e662"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144791883","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}
The incidence of haematological malignancies during pregnancy ranges from 4·0 to 15·8 cases per 100 000 pregnancies, with Hodgkin lymphoma, acute leukaemia, and aggressive B-cell non-Hodgkin lymphoma being the most frequent subtypes. Although survival rates are similar to those in patients who are not pregnant with similar disease profiles, pregnant women face higher risks of maternal morbidity, along with adverse obstetric and neonatal outcomes. Their management, therefore, requires a carefully balanced approach that minimises obstetric risks and ensures effective oncological control. Physiological adaptations of pregnancy can obscure the clinical presentation of sepsis, modulate the course of infections, and, through altered pharmacokinetics, complicate antimicrobial therapy. Safety data on antimicrobials are scarce and concerns about teratogenicity further constrain therapeutic decisions. As a result, infection management in pregnant women requires tailored approaches to diagnosis, antimicrobial therapy, and fetal monitoring. This Review summarises the physiological changes influencing infection risk and treatment efficacy in pregnant women with haematological malignancies; it outlines key challenges in prevention and management and identifies crucial knowledge gaps to guide practice and research in this complex interplay.
{"title":"Prevention and management of infectious diseases in pregnant women with haematological malignancies.","authors":"Sébastien Gaultier,Asmaa Tazi,Caroline Charre,André Paugam,Laurent Chouchana,Sihem Benaboud,Marie Lachâtre,Olivier Baud,Catherine Fischer,Pauline Richebé,Etienne Canouï,Olivia Anselem,Fanny Vuotto,Justine Decroocq,Vassilis Tsatsaris,Didier Bouscary,Rudy Birsen,Caroline Charlier","doi":"10.1016/s2352-3026(25)00165-6","DOIUrl":"https://doi.org/10.1016/s2352-3026(25)00165-6","url":null,"abstract":"The incidence of haematological malignancies during pregnancy ranges from 4·0 to 15·8 cases per 100 000 pregnancies, with Hodgkin lymphoma, acute leukaemia, and aggressive B-cell non-Hodgkin lymphoma being the most frequent subtypes. Although survival rates are similar to those in patients who are not pregnant with similar disease profiles, pregnant women face higher risks of maternal morbidity, along with adverse obstetric and neonatal outcomes. Their management, therefore, requires a carefully balanced approach that minimises obstetric risks and ensures effective oncological control. Physiological adaptations of pregnancy can obscure the clinical presentation of sepsis, modulate the course of infections, and, through altered pharmacokinetics, complicate antimicrobial therapy. Safety data on antimicrobials are scarce and concerns about teratogenicity further constrain therapeutic decisions. As a result, infection management in pregnant women requires tailored approaches to diagnosis, antimicrobial therapy, and fetal monitoring. This Review summarises the physiological changes influencing infection risk and treatment efficacy in pregnant women with haematological malignancies; it outlines key challenges in prevention and management and identifies crucial knowledge gaps to guide practice and research in this complex interplay.","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756079","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 : 2025-07-17DOI: 10.1016/s2352-3026(25)00137-1
Kristina Kirschner,Yael Kusne,Catherine Cargo,Mrinal M Patnaik
Clonal haematopoiesis refers to the presence of somatic mutations in haematopoietic stem and progenitor cells, accompanied by the expansion of high-fitness clones over time. Age-related clonal haematopoiesis arises from ageing-related DNA damage and is associated with haematological neoplasms and coronary artery disease. Genotoxic therapies can promote the selection of somatic mutations, leading to therapy-related clonal haematopoiesis. Clonal haematopoiesis in acquired or inherited bone marrow failure syndromes and germline predispositions leads to clonal expansion, where fitness constraints on haematopoietic stem cells drive mutation acquisition. When clonal haematopoiesis occurs in the context of persistent unexplained cytopenias, with somatic mutations driving haematopoietic dysfunction, it is referred to as clonal cytopenias of undetermined significance (CCUS). CCUS is a precursor to myeloid neoplasms, with variable progression rates. In this Review, we summarise the current state of knowledge, offering critical insights into the molecular evolution of, and diagnostics and risk assessment for clonal haematopoiesis and CCUS. We highlight the interplay between ageing and environmental factors in the progression to haematological neoplasms and discuss challenges for risk stratification and disease monitoring.
{"title":"Clonal haematopoiesis to clonal cytopenias: unravelling disease evolution over time.","authors":"Kristina Kirschner,Yael Kusne,Catherine Cargo,Mrinal M Patnaik","doi":"10.1016/s2352-3026(25)00137-1","DOIUrl":"https://doi.org/10.1016/s2352-3026(25)00137-1","url":null,"abstract":"Clonal haematopoiesis refers to the presence of somatic mutations in haematopoietic stem and progenitor cells, accompanied by the expansion of high-fitness clones over time. Age-related clonal haematopoiesis arises from ageing-related DNA damage and is associated with haematological neoplasms and coronary artery disease. Genotoxic therapies can promote the selection of somatic mutations, leading to therapy-related clonal haematopoiesis. Clonal haematopoiesis in acquired or inherited bone marrow failure syndromes and germline predispositions leads to clonal expansion, where fitness constraints on haematopoietic stem cells drive mutation acquisition. When clonal haematopoiesis occurs in the context of persistent unexplained cytopenias, with somatic mutations driving haematopoietic dysfunction, it is referred to as clonal cytopenias of undetermined significance (CCUS). CCUS is a precursor to myeloid neoplasms, with variable progression rates. In this Review, we summarise the current state of knowledge, offering critical insights into the molecular evolution of, and diagnostics and risk assessment for clonal haematopoiesis and CCUS. We highlight the interplay between ageing and environmental factors in the progression to haematological neoplasms and discuss challenges for risk stratification and disease monitoring.","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144669405","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 : 2025-07-15DOI: 10.1016/s2352-3026(25)00163-2
Vania Hungria,Marek Hus,ChengCheng Fu,Vera Zherebtsova,Christopher Ward,P Joy Ho,Damian Mikulski,Ludmila Muronova,Claudio Cerchione,Angely Loubert,Laurine Bunod,Manal M'Hari,Nick Pirooz,Rachel Rogers,Chee Paul Lin,Sumita Roy-Ghanta,Joanna B Opalinska,Molly Purser,Astrid McKeown,Simon McNamara,Hena Baig,Lydia Eccersley,Farrah Pompilus,María-Victoria Mateos,
BACKGROUNDBelantamab mafodotin, bortezomib, and dexamethasone showed significant progression-free survival benefit compared with daratumumab, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma in the phase 3 DREAMM-7 study. We aimed to evaluate the effect of belantamab mafodotin, bortezomib, and dexamethasone compared with daratumumab, bortezomib, and dexamethasone on health-related quality of life (HRQOL) using various patient-reported outcomes in patients who participated in DREAMM-7.METHODSThis phase 3, open-label, randomised controlled trial, done at 142 hospitals in 20 countries included adult patients aged 18 years or older with relapsed or refractory multiple myeloma who received at least one previous line of therapy and progressed during or after their most recent treatment and had an Eastern Cooperative Oncology Group performance status of 0 to 2. Eligible patients were randomly assigned (1:1) by a central interactive response technology system to receive intravenous belantamab mafodotin (2·5 mg/kg once on day 1 of each 21-day cycle) or intravenous daratumumab (16 mg/kg once a week in cycles 1-3, every 3 weeks in cycles 4-8, and every 4 weeks in cycle 9 and beyond). Patients in both treatment groups also received subcutaneous bortezomib (1·3 mg/m2 on days 1, 4, 8, and 11 of 21-day cycles) and oral or intravenous dexamethasone (20 mg on the day of and day after bortezomib administration) for the first 8 cycles. Treatment continued until progressive disease, unacceptable toxic effects, withdrawal of consent, or death (whichever occurred first). Patient-reported outcomes were secondary and exploratory objectives. Secondary patient-reported outcome endpoints were change from baseline in HRQOL, as measured by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and EORTC QLQ-MY20, and maximum postbaseline score for each item attribute on the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Exploratory patient-reported outcome endpoints included changes from baseline in symptoms and related effects as measured by Ocular Surface Disease Index (OSDI), change from baseline in FACT-GP5 score, and change from baseline in the EQ-5D VAS. EORTC QLQ-C30, EORTC QLQ-MY20, and FACT-GP5 scores were analysed in the intention-to-treat population, and PRO-CTCAE and OSDI vision-related functioning scores were analysed in the safety population (patients who received at least one dose of treatment). Results were summarised using descriptive statistics. Least-squares mean changes from baseline were estimated using a restricted maximum likelihood-based mixed model. This study was registered with ClinicalTrials.gov, NCT04246047, and is ongoing.FINDINGSBetween May 7, 2020, and June 28, 2021, 494 patients were included in the intention-to-treat population of the DREAMM-7 study (median follow-up 28·2 months, IQR 14·6-31·4) and were randomly assigned to either belantamab
{"title":"Patient-reported outcomes with belantamab mafodotin, bortezomib, and dexamethasone versus daratumumab, bortezomib, and dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-7): results from a phase 3, open-label, randomised controlled trial.","authors":"Vania Hungria,Marek Hus,ChengCheng Fu,Vera Zherebtsova,Christopher Ward,P Joy Ho,Damian Mikulski,Ludmila Muronova,Claudio Cerchione,Angely Loubert,Laurine Bunod,Manal M'Hari,Nick Pirooz,Rachel Rogers,Chee Paul Lin,Sumita Roy-Ghanta,Joanna B Opalinska,Molly Purser,Astrid McKeown,Simon McNamara,Hena Baig,Lydia Eccersley,Farrah Pompilus,María-Victoria Mateos, ","doi":"10.1016/s2352-3026(25)00163-2","DOIUrl":"https://doi.org/10.1016/s2352-3026(25)00163-2","url":null,"abstract":"BACKGROUNDBelantamab mafodotin, bortezomib, and dexamethasone showed significant progression-free survival benefit compared with daratumumab, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma in the phase 3 DREAMM-7 study. We aimed to evaluate the effect of belantamab mafodotin, bortezomib, and dexamethasone compared with daratumumab, bortezomib, and dexamethasone on health-related quality of life (HRQOL) using various patient-reported outcomes in patients who participated in DREAMM-7.METHODSThis phase 3, open-label, randomised controlled trial, done at 142 hospitals in 20 countries included adult patients aged 18 years or older with relapsed or refractory multiple myeloma who received at least one previous line of therapy and progressed during or after their most recent treatment and had an Eastern Cooperative Oncology Group performance status of 0 to 2. Eligible patients were randomly assigned (1:1) by a central interactive response technology system to receive intravenous belantamab mafodotin (2·5 mg/kg once on day 1 of each 21-day cycle) or intravenous daratumumab (16 mg/kg once a week in cycles 1-3, every 3 weeks in cycles 4-8, and every 4 weeks in cycle 9 and beyond). Patients in both treatment groups also received subcutaneous bortezomib (1·3 mg/m2 on days 1, 4, 8, and 11 of 21-day cycles) and oral or intravenous dexamethasone (20 mg on the day of and day after bortezomib administration) for the first 8 cycles. Treatment continued until progressive disease, unacceptable toxic effects, withdrawal of consent, or death (whichever occurred first). Patient-reported outcomes were secondary and exploratory objectives. Secondary patient-reported outcome endpoints were change from baseline in HRQOL, as measured by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and EORTC QLQ-MY20, and maximum postbaseline score for each item attribute on the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Exploratory patient-reported outcome endpoints included changes from baseline in symptoms and related effects as measured by Ocular Surface Disease Index (OSDI), change from baseline in FACT-GP5 score, and change from baseline in the EQ-5D VAS. EORTC QLQ-C30, EORTC QLQ-MY20, and FACT-GP5 scores were analysed in the intention-to-treat population, and PRO-CTCAE and OSDI vision-related functioning scores were analysed in the safety population (patients who received at least one dose of treatment). Results were summarised using descriptive statistics. Least-squares mean changes from baseline were estimated using a restricted maximum likelihood-based mixed model. This study was registered with ClinicalTrials.gov, NCT04246047, and is ongoing.FINDINGSBetween May 7, 2020, and June 28, 2021, 494 patients were included in the intention-to-treat population of the DREAMM-7 study (median follow-up 28·2 months, IQR 14·6-31·4) and were randomly assigned to either belantamab","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144664227","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 : 2025-06-27DOI: 10.1016/s2352-3026(25)00139-5
Prof Shaji K Kumar MD, Prof Simon J Harrison PhD, Prof Michele Cavo MD, Prof Javier de la Rubia MD, Rakesh Popat FRCPath, Prof Cristina Gasparetto MD, Prof Vania Hungria MD, Hans Salwender MD, Prof Kenshi Suzuki MD, Prof Inho Kim MD, Maika Onishi MD, Grace Ku MD, Rajvineeth Pothacamury MD, Muhammad Jalaluddin PhD, Jiewei Zeng PhD, Jeremy A Ross PhD, Edyta Dobkowska MD, Prof Philippe Moreau MD
The phase 3 BELLINI primary endpoint was met, showing superior progression-free survival with venetoclax versus placebo plus bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma as assessed by an independent review committee. However, venetoclax showed increased early mortality. Here, we report the final overall survival analysis.
{"title":"Venetoclax or placebo in combination with bortezomib and dexamethasone in relapsed or refractory multiple myeloma (BELLINI): final overall survival results from a randomised, phase 3 study","authors":"Prof Shaji K Kumar MD, Prof Simon J Harrison PhD, Prof Michele Cavo MD, Prof Javier de la Rubia MD, Rakesh Popat FRCPath, Prof Cristina Gasparetto MD, Prof Vania Hungria MD, Hans Salwender MD, Prof Kenshi Suzuki MD, Prof Inho Kim MD, Maika Onishi MD, Grace Ku MD, Rajvineeth Pothacamury MD, Muhammad Jalaluddin PhD, Jiewei Zeng PhD, Jeremy A Ross PhD, Edyta Dobkowska MD, Prof Philippe Moreau MD","doi":"10.1016/s2352-3026(25)00139-5","DOIUrl":"https://doi.org/10.1016/s2352-3026(25)00139-5","url":null,"abstract":"The phase 3 BELLINI primary endpoint was met, showing superior progression-free survival with venetoclax versus placebo plus bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma as assessed by an independent review committee. However, venetoclax showed increased early mortality. Here, we report the final overall survival analysis.","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515552","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 : 2025-06-25DOI: 10.1016/s2352-3026(25)00117-6
Prof Niels W C J van de Donk MD, Philippe Moreau MD, Jesús F San-Miguel MD, Maria-Victoria Mateos MD, Meletios A Dimopoulos MD, Sonja Zweegman MD, Francesca Gay MD, Monika Engelhardt MD, Roberto Mina MD, Elena Zamagni MD, Michel Delforge MD, Meral Beksac MD, Andrew Spencer MD, Fredrik Schjesvold MD, Christoph Driessen MD, Martin Kaiser MD, Aurore Perrot MD, Ralph Wäsch MD, Charlotte LBM Korst MD, Annemiek Broijl MD, Cyrille Touzeau MD, Salomon Manier MD, Roman Hajek MD, Heinz Ludwig MD, Carlos Fernandez de Larrea MD, Rakesh Popat MD, Pellegrino Musto MD, Paula Rodriguez-Otero MD, Kwee Yong MD, Leo Rasche MD, Evangelos Terpos MD, Marc S Raab MD, Mario Boccadoro MD, Pieter Sonneveld MD, Hermann Einsele MD, EMN Guidelines Committee
Novel T-cell immunotherapies (chimeric antigen receptor [CAR] T cells and T-cell redirecting bispecific antibodies) are changing the treatment landscape of relapsed or refractory multiple myeloma. In this Review, the European Myeloma Network provides recommendations to optimise both safety and efficacy of T-cell immunotherapy. In patients who are eligible for both CAR T-cell therapy and bispecific antibodies, we recommend using CAR T-cell therapy first due to the high response rate and durable progression-free survival, accompanied by improved quality of life. Furthermore, previous bispecific antibody treatment has a negative effect on the efficacy of CAR T-cell therapy, and there is emerging evidence that suggests that relapse after B-cell maturation antigen-directed CAR T-cell therapy can be effectively managed with bispecific antibodies. Timely referral and planning are crucial before initiating T-cell immunotherapy to optimise treatment selection, conduct adequate diagnostic tests (eg, excluding latent infections), and identify modifiable risk factors to improve clinical outcomes. Supportive care is crucial in all patients receiving T-cell immunotherapy to prevent non-relapse mortality.
{"title":"Optimising T-cell immunotherapy in patients with multiple myeloma: practical considerations from the European Myeloma Network","authors":"Prof Niels W C J van de Donk MD, Philippe Moreau MD, Jesús F San-Miguel MD, Maria-Victoria Mateos MD, Meletios A Dimopoulos MD, Sonja Zweegman MD, Francesca Gay MD, Monika Engelhardt MD, Roberto Mina MD, Elena Zamagni MD, Michel Delforge MD, Meral Beksac MD, Andrew Spencer MD, Fredrik Schjesvold MD, Christoph Driessen MD, Martin Kaiser MD, Aurore Perrot MD, Ralph Wäsch MD, Charlotte LBM Korst MD, Annemiek Broijl MD, Cyrille Touzeau MD, Salomon Manier MD, Roman Hajek MD, Heinz Ludwig MD, Carlos Fernandez de Larrea MD, Rakesh Popat MD, Pellegrino Musto MD, Paula Rodriguez-Otero MD, Kwee Yong MD, Leo Rasche MD, Evangelos Terpos MD, Marc S Raab MD, Mario Boccadoro MD, Pieter Sonneveld MD, Hermann Einsele MD, EMN Guidelines Committee","doi":"10.1016/s2352-3026(25)00117-6","DOIUrl":"https://doi.org/10.1016/s2352-3026(25)00117-6","url":null,"abstract":"Novel T-cell immunotherapies (chimeric antigen receptor [CAR] T cells and T-cell redirecting bispecific antibodies) are changing the treatment landscape of relapsed or refractory multiple myeloma. In this Review, the European Myeloma Network provides recommendations to optimise both safety and efficacy of T-cell immunotherapy. In patients who are eligible for both CAR T-cell therapy and bispecific antibodies, we recommend using CAR T-cell therapy first due to the high response rate and durable progression-free survival, accompanied by improved quality of life. Furthermore, previous bispecific antibody treatment has a negative effect on the efficacy of CAR T-cell therapy, and there is emerging evidence that suggests that relapse after B-cell maturation antigen-directed CAR T-cell therapy can be effectively managed with bispecific antibodies. Timely referral and planning are crucial before initiating T-cell immunotherapy to optimise treatment selection, conduct adequate diagnostic tests (eg, excluding latent infections), and identify modifiable risk factors to improve clinical outcomes. Supportive care is crucial in all patients receiving T-cell immunotherapy to prevent non-relapse mortality.","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515551","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 : 2025-06-15DOI: 10.1016/s2352-3026(25)00144-9
Prof Elias Jabbour MD, Federico Lussana MD, Pilar Martínez-Sánchez MD, Anna Torrent MD, José J Rifón MD, Vaibhav Agrawal MD, Mar Tormo MD, Ryan D Cassaday MD, Thomas Cluzeau MD, Françoise Huguet MD, Cristina Papayannidis MD, Jesús M Hernández-Rivas MD, Anita Rijneveld MD, Shaun Fleming MD, Vladan Vucinic MD, Boris Böll MD, Takayuki Ikezoe MD, Maher Abdul-Hay MD, Mary L Savoie MD, Andre C Schuh MD, Celine Berthon MD, Stefan Schwartz MD, Sabina Chiaretti MD, Junichiro Yuda MD, Takuya Miyazaki MD, José González-Campos MD, Yuqi Chen PhD, Hansen Wong PhD, Jessica Choudhry PharmD, Gerhard Zugmaier MD, Erin Guest MD, Paul Gordon MD, Prof Hagop Kantarjian MD
Two doses of subcutaneous blinatumomab in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia were identified as preliminary recommended phase 2 doses, based on the dose-escalation phase of this multicentre single-arm, phase 1/2 trial. Here, we aim to further study the safety, activity, and pharmacokinetics of these doses in all participants who have received them, including those treated in the completed phase 1b expansion part of the study.
{"title":"Subcutaneous blinatumomab in adults with relapsed or refractory B-cell acute lymphoblastic leukaemia: post-hoc safety and activity analysis from a multicentre, single-arm, phase 1/2 trial","authors":"Prof Elias Jabbour MD, Federico Lussana MD, Pilar Martínez-Sánchez MD, Anna Torrent MD, José J Rifón MD, Vaibhav Agrawal MD, Mar Tormo MD, Ryan D Cassaday MD, Thomas Cluzeau MD, Françoise Huguet MD, Cristina Papayannidis MD, Jesús M Hernández-Rivas MD, Anita Rijneveld MD, Shaun Fleming MD, Vladan Vucinic MD, Boris Böll MD, Takayuki Ikezoe MD, Maher Abdul-Hay MD, Mary L Savoie MD, Andre C Schuh MD, Celine Berthon MD, Stefan Schwartz MD, Sabina Chiaretti MD, Junichiro Yuda MD, Takuya Miyazaki MD, José González-Campos MD, Yuqi Chen PhD, Hansen Wong PhD, Jessica Choudhry PharmD, Gerhard Zugmaier MD, Erin Guest MD, Paul Gordon MD, Prof Hagop Kantarjian MD","doi":"10.1016/s2352-3026(25)00144-9","DOIUrl":"https://doi.org/10.1016/s2352-3026(25)00144-9","url":null,"abstract":"Two doses of subcutaneous blinatumomab in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia were identified as preliminary recommended phase 2 doses, based on the dose-escalation phase of this multicentre single-arm, phase 1/2 trial. Here, we aim to further study the safety, activity, and pharmacokinetics of these doses in all participants who have received them, including those treated in the completed phase 1b expansion part of the study.","PeriodicalId":501011,"journal":{"name":"The Lancet Haematology","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144305091","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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