Pub Date : 2025-04-01Epub Date: 2025-03-05DOI: 10.1016/S2352-3026(25)00039-0
Eva Domingo Domenech
{"title":"Peripheral T-cell lymphoma in the Latin American population.","authors":"Eva Domingo Domenech","doi":"10.1016/S2352-3026(25)00039-0","DOIUrl":"10.1016/S2352-3026(25)00039-0","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e233-e234"},"PeriodicalIF":15.4,"publicationDate":"2025-04-01","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}
Pub Date : 2025-04-01DOI: 10.1016/S2352-3026(25)00069-9
Francesca Romana Mauro
{"title":"Improving SARS-CoV-2 vaccine response is challenging in chronic lymphocytic leukaemia.","authors":"Francesca Romana Mauro","doi":"10.1016/S2352-3026(25)00069-9","DOIUrl":"10.1016/S2352-3026(25)00069-9","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"12 4","pages":"e238-e239"},"PeriodicalIF":15.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774699","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 : 2025-04-01Epub Date: 2025-03-12DOI: 10.1016/S2352-3026(24)00384-3
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
Background: 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.
Methods: 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.
Findings: 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%]).
Interpretation: 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.
{"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":"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":"e248-e257"},"PeriodicalIF":17.7,"publicationDate":"2025-04-01","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}
Pub Date : 2025-04-01Epub Date: 2025-03-05DOI: 10.1016/S2352-3026(25)00011-0
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
<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Findings: </strong>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<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<0·0001) and Mexico (22 [31%] of 70 patients; p<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
背景：外周t细胞淋巴瘤是一种罕见且异质性的成熟t细胞肿瘤，其特征为侵袭性行为。先前评估拉丁美洲周围t细胞淋巴瘤流行病学的研究在该地区大多数国家的代表性受到限制。在这项研究中，我们旨在描述整个拉丁美洲的外周t细胞淋巴瘤流行病学。方法：我们对拉丁美洲11个国家（阿根廷、巴西、智利、哥伦比亚、古巴、危地马拉、墨西哥、巴拉圭、秘鲁、乌拉圭和委内瑞拉）新诊断的外周t细胞淋巴瘤患者（年龄≥18岁）进行了一项国际、回顾性、队列研究。我们使用了拉丁美洲研究中心（Grupo de Estudio Latinoamericano de linfoprolifativos）基于医院的登记处(回顾性登记处；2000年1月1日至2023年6月30日)、巴西t细胞项目（回顾性研究从2015年1月1日至2017年6月30日，前瞻性研究从2017年7月1日至2023年6月30日）和国际t细胞淋巴瘤项目（前瞻性登记）。主要结果是外周t细胞淋巴瘤亚型的患病率，使用Kaplan-Meier法估计的总生存率和客观缓解率。使用Kaplan-Meier法估计生存概率，并与log-rank检验进行比较。总有效率由完全和部分反应的总和计算，95% ci使用Clopper-Pearson方法估计。结果：2000年至2023年间，1979例病理诊断为外周t细胞淋巴瘤的患者符合我们的分布分析纳入标准，1349例纳入治疗模式和结局分析。诊断时中位年龄54岁（IQR 41-67）， 1794例患者中733例（41%）为女性，1061例（59%）为男性。最常见的亚型是外周t细胞淋巴瘤（1979例患者中有688例[35%]）；第二和第三常见亚型是成人t细胞白血病或淋巴瘤（1979例患者中有333例[17%]）和结外自然杀伤t细胞淋巴瘤（1979例患者中有291例[15%]）。其次是alk阴性间变性大t细胞淋巴瘤（186例（9%））、成熟t细胞淋巴瘤（163例（8%））、血管免疫母细胞t细胞淋巴瘤（123例（6%））和alk阳性间变性大t细胞淋巴瘤（73例（4%））。秘鲁观察到的成人t细胞白血病或淋巴瘤患者比例较高(414例患者中有158例[39%]；结论：我们的研究强调了拉丁美洲外周t细胞淋巴瘤的独特流行病学特征，成人t细胞白血病或淋巴瘤和结外自然杀伤t细胞淋巴瘤的患病率很高。这些发现提供了一个重要的机会，通过将拉丁美洲国家纳入全球研究，优先考虑这些罕见的外周t细胞淋巴瘤亚型的临床试验。然而，我们的发现需要在强有力的流行病学研究中进一步验证。资助：美国血液学学会哈罗德·阿莫斯医学院发展计划奖和罗伯特·A·温临床试验多样性计划奖。翻译：有关摘要的葡萄牙语和西班牙语翻译，请参阅补充资料部分。
{"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":"10.1016/S2352-3026(25)00011-0","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Findings: </strong>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<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<0·0001) and Mexico (22 [31%] of 70 patients; p<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":"e258-e268"},"PeriodicalIF":15.4,"publicationDate":"2025-04-01","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}
Pub Date : 2025-04-01Epub Date: 2025-03-13DOI: 10.1016/S2352-3026(25)00040-7
Luca Paruzzo, Marco Ruella
{"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":"e236-e238"},"PeriodicalIF":15.4,"publicationDate":"2025-04-01","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}
Pub Date : 2025-04-01Epub Date: 2025-03-13DOI: 10.1016/S2352-3026(24)00385-5
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
<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 198 (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 com
{"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":"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 198 (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 com","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e269-e281"},"PeriodicalIF":15.4,"publicationDate":"2025-04-01","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}
Pub Date : 2025-04-01Epub Date: 2025-03-12DOI: 10.1016/S2352-3026(25)00033-X
Sebastian Mendez-Marti, Swee Lay Thein
{"title":"Now where do we STAND with crizanlizumab?","authors":"Sebastian Mendez-Marti, Swee Lay Thein","doi":"10.1016/S2352-3026(25)00033-X","DOIUrl":"10.1016/S2352-3026(25)00033-X","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e232-e233"},"PeriodicalIF":17.7,"publicationDate":"2025-04-01","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}
Pub Date : 2025-04-01Epub Date: 2025-03-13DOI: 10.1016/S2352-3026(25)00009-2
Susan Bal
{"title":"Monumen-TAL progress in the treatment of relapsed multiple myeloma.","authors":"Susan Bal","doi":"10.1016/S2352-3026(25)00009-2","DOIUrl":"10.1016/S2352-3026(25)00009-2","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e235-e236"},"PeriodicalIF":15.4,"publicationDate":"2025-04-01","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}
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