Lancet Haematology最新文献

{"title":"Talicabtagene autoleucel for relapsed or refractory B-cell malignancies: results from an open-label, multicentre, phase 1/2 study.","authors":"Hasmukh Jain, Atharva Karulkar, Devanshi Kalra, Smrithi Ravikumar, Shreshtha Shah, Afrin Firfiray, Juber Pendhari, Ankesh Kumar Jaiswal, Aalia Khan, Manivasagam Sundharam, Anand Vaibhaw, Ashish Saroha, Shreewardhan Rajyopadhye, Moumita Basu, Sweety Asija, Ambalika Chowdhury, Rohit Beher, Ankit Banik, Alka Dwivedi, Shalini Purwar, Gaurav Narula, Shripad Banavali, Nitin Jain, Steven L Highfill, David Stroncek, Terry Fry, Sameer Melinkeri, Lovin Wilson, Narendra Agarwal, Anil Aribandi, Pavan Kumar Boyella, Nirali N Shah, Sattva S Neelapu, Manju Sengar, Rahul Purwar","doi":"10.1016/S2352-3026(24)00377-6","DOIUrl":"https://doi.org/10.1016/S2352-3026(24)00377-6","url":null,"abstract":"<p><strong>Background: </strong>In low-income and middle-income counties (LMICs), the outcome of relapsed or refractory B-cell malignancies is poor due to the absence of effective therapies. We report the results of a phase 1/2 study of a novel humanised anti-CD19 4-1BB chimeric antigen receptor (CAR) T-cell therapy, talicabtagene autoleucel, for patients with relapsed or refractory B-cell malignancies.</p><p><strong>Methods: </strong>This open-label, multicentre, phase 1/2 study was done at six tertiary cancer centres in India. Phase 1 was a single-centre study done in Tata Memorial Hospital, India, in patients aged 18 years or older with relapsed or refractory B-cell lymphomas. Phase 2 was a single-arm, multicentre, basket trial done in five tertiary cancer centres in patients aged 15 years and older with relapsed or refractory B-cell acute lymphoblastic leukaemia or B-cell lymphoma. Eligible patients had a life expectancy of 12 weeks or more, an ECOG performance status of 0-1 (phase 1) or 0-2 (phase 2), and an adequate organ function. Patients underwent apheresis to obtain at least 1 × 10<sup>9</sup> lymphocytes to manufacture CAR T cells. Lymphodepletion therapy was done with cyclophosphamide 500 mg/m<sup>2</sup> and fludarabine 30 mg/m<sup>2</sup> for 3 days or bendamustine 90 mg/m<sup>2</sup> for 2 days. Patients were then infused intravenously with talicabtagene autoleucel 1 × 10<sup>7</sup>-5 × 10<sup>9</sup> CAR T cells in a fractionated schedule (10%, 30%, and 60%, on days 0, 1, and 2, respectively) during phase 1 or at least 5 × 10<sup>6</sup> CAR T cells per kg (up to 2 × 10<sup>9</sup> CAR T cells) on day 0 during phase 2. The primary endpoints were safety (phase 1) and overall response rate (phase 2). The efficacy analysis was done in the efficacy evaluable cohort (all patients who received the target dose and 3 days of lymphodepletion therapy). The safety analysis was done in the safety population (all patients who received talicabtagene autoleucel). The trials are registered with Clinical Trial Registry-India (CTRI/2021/04/032727 and CTRI/2022/12/048211), and enrolment is closed.</p><p><strong>Findings: </strong>Of 64 patients, 14 were enrolled in phase 1 (from May 11, 2021, to May 13, 2022) and 50 were enrolled in phase 2 (Dec 27, 2022, to Aug 31, 2023). The median age of the overall cohort was 44 years (IQR 27-57), and 49 (77%) of 64 patients were male and 15 (23%) were female. In phase 1, no dose-limiting toxicities occurred at doses of 2 × 10<sup>6</sup>-17 × 10<sup>6</sup> CAR T cells per kg. A dose of at least 5 × 10<sup>6</sup> CAR T cells per kg was chosen for phase 2 based on a complete response in three of seven patients at this dose. The most common grade 3 or worse toxicities were haematological events: anaemia (35 [61%] of 57 patients), thrombocytopenia (37 [65%] patients), neutropenia (55 [96%] patients, and febrile neutropenia (27 [47%]) patients). There were two treatment-related deaths, one due to febrile neutrope","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":""},"PeriodicalIF":15.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and activity of talquetamab in patients with relapsed or refractory multiple myeloma (MonumenTAL-1): a multicentre, open-label, phase 1-2 study.","authors":"Ajai Chari, Cyrille Touzeau, Carolina Schinke, Monique C Minnema, Jesus G Berdeja, Albert Oriol, Niels W C J van de Donk, Paula Rodríguez-Otero, Daniel Morillo, Carmen Martinez-Chamorro, María-Victoria Mateos, Luciano J Costa, Jo Caers, Leo Rasche, Amrita Krishnan, Jing Christine Ye, Lionel Karlin, Brea Lipe, Deeksha Vishwamitra, Sheri Skerget, Raluca Verona, Xuewen Ma, Xiang Qin, Hein Ludlage, Michela Campagna, Tara Masterson, Brandi Hilder, Jaszianne Tolbert, Thomas Renaud, Jenna D Goldberg, Colleen Kane, Christoph Heuck, Jesus San-Miguel, Philippe Moreau","doi":"10.1016/S2352-3026(24)00385-5","DOIUrl":"https://doi.org/10.1016/S2352-3026(24)00385-5","url":null,"abstract":"<p><strong>Background: </strong>Talquetamab is the first GPRC5D × CD3 bispecific antibody approved for relapsed or refractory multiple myeloma. In phase 1 of the MonumenTAL-1 study, initial results of subcutaneous talquetamab 0·4 mg/kg once a week and 0·8 mg/kg every 2 weeks showed preliminary clinical activity. We describe safety and activity results in patients treated with talquetamab, including patients who had received previous T-cell redirection therapy (TCR). This post-hoc analysis was done with more mature median follow-up to evaluate duration of response in patients treated with talquetamab 0·8 mg/kg every 2 weeks.</p><p><strong>Methods: </strong>MonumenTAL-1 is a multicentre, open-label, phase 1-2 study of talquetamab, phase 1 of which has previously been published. The 0·4 mg/kg once a week and 0·8 mg/kg every 2 weeks recommended subcutaneous doses identified in phase 1 were evaluated in phase 2 in patients who were 18 years of age or older, had at least three previous lines of therapy, had an Eastern Cooperative Oncology Group performance status of 0 to 2, and were naive or exposed to previous TCR. The primary endpoint was overall response rate assessed by independent review committee in all patients who received at least one dose of talquetamab. Safety was assessed in all patients who received at least one dose of talquetamab. This study was registered with ClinicalTrials.gov, NCT03399799 (phase 1) and NCT04634552 (phase 2).</p><p><strong>Findings: </strong>Between Jan 3, 2018, and Feb 20, 2023, 735 patients were screened across all phase 1-2 cohorts. Of these, 537 patients screened for inclusion were treated across phase 1 and 2 cohorts, of whom 1983 (27%) patients were excluded from the study, most commonly due to not meeting eligibility criteria or not having measurable disease. As of Oct 11, 2023, 375 patients had received recommended talquetamab doses across three groups: 143 (0·4 mg/kg once a week group) and 154 (0·8 mg/kg every 2 weeks group) TCR-naive patients and 78 with previous TCR who received either recommended dose (previous TCR group). 217 (58%) of 375 patients were male and 158 (42%) were female. 325 (87%) of 375 patients were White and 32 (9%) patients were Black. Median follow-up was 25·6 months (IQR 8·5-25·9) in the 0·4 mg/kg once a week group, 19·4 months (9·2-20·7) in the 0·8 mg/kg every 2 weeks group, and 16·8 months (7·6-18·7) in the previous TCR group. Overall response rate was 74% (106 of 143 patients, 95% CI 66-81) in the 0·4 mg/kg once a week group, 69% (107 of 154 patients, 62-77) in the 0·8 mg/kg every 2 weeks group, and 67% (52 of 78 patients, 55-77) in the previous TCR group. Most common adverse events in the 0·4 mg/kg once a week, 0·8 mg/kg every 2 weeks, and previous TCR groups were cytokine release syndrome (113 [79%] of 143 patients, 115 [75%] of 154 patients, and 57 [73%] of 78 patients), taste changes (103 [72%], 110 [71%], and 59 [76%]), and infections (85 [59%], 105 [68%], and 59 [76%]). Most co","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":""},"PeriodicalIF":15.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAR T-cell therapy in LMICs: approval of talicabtagene autoleucel in India.","authors":"Luca Paruzzo, Marco Ruella","doi":"10.1016/S2352-3026(25)00040-7","DOIUrl":"10.1016/S2352-3026(25)00040-7","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":""},"PeriodicalIF":15.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monumen-TAL progress in the treatment of relapsed multiple myeloma.","authors":"Susan Bal","doi":"10.1016/S2352-3026(25)00009-2","DOIUrl":"https://doi.org/10.1016/S2352-3026(25)00009-2","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":""},"PeriodicalIF":15.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crizanlizumab with or without hydroxyurea in patients with sickle cell disease (STAND): primary analyses from a placebo-controlled, randomised, double-blind, phase 3 trial.","authors":"Miguel R Abboud, Rodolfo D Cançado, Mariane De Montalembert, Wally R Smith, Hala Rimawi, Ersi Voskaridou, Birol Güvenç, Kenneth I Ataga, Deborah Keefe, Kai Grosch, Jimmy Watson, Evgeniya Reshetnyak, Michele L Nassin, Yvonne Dei-Adomakoh","doi":"10.1016/S2352-3026(24)00384-3","DOIUrl":"https://doi.org/10.1016/S2352-3026(24)00384-3","url":null,"abstract":"<p><strong>Background: </strong>Crizanlizumab has previously shown efficacy as a potent disease-modifying therapy for alleviating vaso-occlusive crisis in sickle cell disease. The SUSTAIN study showed a reduction of vaso-occlusive crises in patients treated with 5 mg/kg crizanlizumab, compared with placebo. The STAND study aimed to evaluate the efficacy and safety of two doses (5·0 mg/kg and 7·5 mg/kg) of crizanlizumab in sickle cell disease. Herein, we report the primary analysis results of STAND.</p><p><strong>Methods: </strong>STAND is a phase 3, multicentre, randomised, double-blind study of patients with sickle cell disease aged 12 years and older done at 65 sites in 21 countries. Patients were randomly assigned (1:1:1) to receive either 5·0 mg/kg of crizanlizumab, 7·5 mg/kg of crizanlizumab, or placebo, in addition to standard of care, for 1 year. The primary endpoint was the annualised rate of vaso-occlusive crises leading to a health-care visit over the first-year post-randomisation. The secondary objectives included assessing crizanlizumab's safety. The trial is registered at ClinicalTrials.gov (NCT03814746) and is ongoing.</p><p><strong>Findings: </strong>Between July 26, 2019, and Aug 31, 2022, 252 patients were enrolled and treated. The primary analysis showed an adjusted annualised rate of vaso-occlusive crises of 2·49 (95% CI 1·90-3·26) in the crizanlizumab 5·0 mg/kg group, 2·04 (1·56-2·65) in the 7·5 mg/kg group, and 2·30 (1·75-3·01) in the placebo group. Ratios of adjusted annualised rates of vaso-occlusive crises leading to health-care visits were 1·08 (95% CI 0·76-1·55, p>0·999) for 5·0 mg/kg and 0·89 (0·62-1·27, p>0·999) for 7·5 mg/kg vs placebo. The incidence of adverse events was similar across treatment groups. Grade 3 or higher adverse events were observed less frequently in the placebo and crizanlizumab 7·5 mg/kg groups (27 [32%] of 85 and 32 [39%] of 83, respectively) than in the 5·0 mg/kg group (47 [56%] of 84). Serious adverse events (all grades) were also less frequent in the placebo and crizanlizumab 7·5 mg/kg groups (26 [31%] and 22 [27%], respectively) than in the 5·0 mg/kg group (35 [42%]).</p><p><strong>Interpretation: </strong>The STAND study supports the safety and tolerability of crizanlizumab in the treatment of sickle cell disease. The primary analysis showed no significant difference in efficacy between crizanlizumab and placebo. Factors including the COVID-19 pandemic, global enrolment with varied patterns of health-care use and vaso-occlusive crisis management as well as the commercial availability of crizanlizumab might have influenced these results. The safety profile of crizanlizumab was consistent with that in previous reports, without new safety concerns.</p><p><strong>Funding: </strong>Novartis Pharmaceuticals.</p>","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":""},"PeriodicalIF":15.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Now where do we STAND with crizanlizumab?","authors":"Sebastian Mendez-Marti, Swee Lay Thein","doi":"10.1016/S2352-3026(25)00033-X","DOIUrl":"https://doi.org/10.1016/S2352-3026(25)00033-X","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":""},"PeriodicalIF":15.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral T-cell lymphoma in the Latin American population.","authors":"Eva Domingo Domenech","doi":"10.1016/S2352-3026(25)00039-0","DOIUrl":"https://doi.org/10.1016/S2352-3026(25)00039-0","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":""},"PeriodicalIF":15.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiology, clinical features, and outcomes of peripheral T-cell lymphoma in Latin America: an international, retrospective, cohort study.","authors":"Luis Malpica, Henry Idrobo, Astrid Pavlovsky, Eliana C M Miranda, Denisse Castro, Brady Beltran, Daniel J Enriquez, Jule F Vasquez, Claudia Roche, Fabiola Valvert, Luis Villela, Thais Fischer, Juliana Pereira, Renata L R Baptista, Guilherme Duffles, Sergio A B Brasil, Carolina Oliver, Jamila Vaz Tavarez, Fernando Warley, Lorena Fiad, Laura Korin, Patricio H Pereyra, Macarena Roa, Maria A Torres, Carolina V Mahuad, Alfredo R Quiroz, Raimundo Gazitua, Massimo Federico, Bryan Valcarcel, Carlos Chiattone","doi":"10.1016/S2352-3026(25)00011-0","DOIUrl":"https://doi.org/10.1016/S2352-3026(25)00011-0","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Peripheral T-cell lymphomas represent a rare and heterogeneous group of mature T-cell neoplasms characterised by aggressive behavior. Previous studies evaluating peripheral T-cell lymphoma epidemiology across Latin America have been restricted in their representation of most countries in the region. In this study, we aimed to describe peripheral T-cell lymphoma epidemiology across Latin America.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We did an international, retrospective, cohort study of patients (aged ≥18 years) with newly diagnosed peripheral T-cell lymphoma across 11 countries in Latin America (Argentina, Brazil, Chile, Colombia, Cuba, Guatemala, Mexico, Paraguay, Peru, Uruguay, and Venezuela). We used the hospital-based registries of the Grupo de Estudio Latinoamericano de Linfoproliferativos (retrospective registry; Jan 1, 2000, to June 30, 2023), the Brazilian T-cell Project (retrospective from Jan 1, 2015, to June 30, 2017 and prospective from July 1, 2017, to June 30, 2023), and the International T-cell Lymphoma Project (prospective registry). The main outcomes were prevalence of peripheral T-cell lymphoma subtypes, overall survival, estimated using the Kaplan-Meier method, and objective response rate. Survival probabilities were estimated using the Kaplan-Meier method and compared with the log-rank test. Overall response rate was calculated by summing complete and partial responses, with 95% CIs estimated using the Clopper-Pearson method.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;1979 patients diagnosed with peripheral T-cell lymphoma by pathology, between 2000 and 2023, met our inclusion criteria for the distribution analysis and 1349 were included in the treatment patterns and outcome analysis. Median age at diagnosis was 54 years (IQR 41-67), 733 (41%) of 1794 patients were female, and 1061 (59%) patients were male. The most common subtype was peripheral T-cell lymphoma, not otherwise specified (688 [35%] of 1979 patients); the second and third most frequent subtypes were adult T-cell leukaemia or lymphoma (333 [17%] of 1979 patients) and extranodal natural killer T-cell lymphoma (291 [15%] of 1979 patients). The next most common subtypes were ALK-negative anaplastic large T-cell lymphoma (186 [9%] of 1979 patients), mature T-cell lymphoma, not otherwise specified (163 [8%] of 1979), angioimmunoblastic T-cell lymphoma (123 [6%] of 1979 patients), and ALK-positive anaplastic large T-cell lymphoma (73 [4%] of 1979 patients). The observed proportion of people with adult T-cell leukaemia or lymphoma was higher in Peru (158 [39%] of 414 patients; p&lt;0·0001) and Colombia (17 [29%] of 58 patients; p=0·011), whereas the percentage for extranodal natural killer T-cell lymphoma was higher in Central America and the Caribbean (105 [41%] of 255 patients; p&lt;0·0001) and Mexico (22 [31%] of 70 patients; p&lt;0·0001). With a median follow-up of 36 months (IQR 12-60) in the analytical cohort, we observed 674 deaths, and 3-year overall sur","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":""},"PeriodicalIF":15.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fine-tuning of haploidentical haematopoietic stem cell transplantation.","authors":"Yoshinobu Kanda","doi":"10.1016/S2352-3026(25)00012-2","DOIUrl":"10.1016/S2352-3026(25)00012-2","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e165-e167"},"PeriodicalIF":15.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to Lancet Haematol 2025; 12: e190-200.","authors":"","doi":"10.1016/S2352-3026(25)00045-6","DOIUrl":"https://doi.org/10.1016/S2352-3026(25)00045-6","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"12 3","pages":"e175"},"PeriodicalIF":15.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568584","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}