Lancet HaematologyPub Date : 2024-10-01DOI: 10.1016/S2352-3026(24)00287-4
Jacqueline Del Castillo
{"title":"Lines of the haematology community.","authors":"Jacqueline Del Castillo","doi":"10.1016/S2352-3026(24)00287-4","DOIUrl":"https://doi.org/10.1016/S2352-3026(24)00287-4","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":null,"pages":null},"PeriodicalIF":15.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394381","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}
Lancet HaematologyPub Date : 2024-10-01Epub Date: 2024-07-23DOI: 10.1016/S2352-3026(24)00176-5
Dian Zhou, Qian Sun, Jieyun Xia, Weiying Gu, Jun Qian, Wanchuan Zhuang, Zhiling Yan, Hai Cheng, Wei Chen, Feng Zhu, Kunming Qi, Depeng Li, Wei Sang, Lili Zhu, Sha Ma, Hujun Li, Huanxin Zhang, Tingting Qiu, Dongmei Yan, Yanlei Zhang, Shuixiu Peng, Alex H Chang, Kailin Xu, Zhenyu Li
{"title":"Anti-BCMA/GPRC5D bispecific CAR T cells in patients with relapsed or refractory multiple myeloma: a single-arm, single-centre, phase 1 trial.","authors":"Dian Zhou, Qian Sun, Jieyun Xia, Weiying Gu, Jun Qian, Wanchuan Zhuang, Zhiling Yan, Hai Cheng, Wei Chen, Feng Zhu, Kunming Qi, Depeng Li, Wei Sang, Lili Zhu, Sha Ma, Hujun Li, Huanxin Zhang, Tingting Qiu, Dongmei Yan, Yanlei Zhang, Shuixiu Peng, Alex H Chang, Kailin Xu, Zhenyu Li","doi":"10.1016/S2352-3026(24)00176-5","DOIUrl":"10.1016/S2352-3026(24)00176-5","url":null,"abstract":"<p><strong>Background: </strong>Some challenges still exist with single-target B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapies due to variable or negative BCMA expression, although they have yielded remarkable efficacy in relapsed or refractory multiple myeloma. We developed anti-BCMA/GPRC5D bispecific CARs to mitigate the limitations and potentiate the functions of CAR T cells.</p><p><strong>Methods: </strong>This single-arm, phase 1 trial was conducted at the Affiliated Hospital of Xuzhou Medical University (Xuzhou, China). The trial enrolled patients aged 18-75 years with relapsed or refractory multiple myeloma and an Eastern Cooperative Oncology Group performance status of 0-3. Anti-BCMA/GPRC5D bispecific CAR T cells were administered at 0·5 × 10<sup>6</sup>, 1·0 × 10<sup>6</sup>, 2·0 × 10<sup>6</sup>, and 4·0 × 10<sup>6</sup> CAR T cells per kg in the dose-escalation phase, with additional patients included at the dose selected for the dose-expansion phase. The primary endpoint was safety, which included dose-limiting toxicity and maximum tolerated dose. Activity was also evaluated as a secondary endpoint. The maximum tolerated dose was chosen for the dose-expansion phase. Safety and activity analyses were done in all patients who received anti-BCMA/GPRC5D bispecific CAR T cells as defined in the protocol. This trial is registered with ClinicalTrials.gov (NCT05509530) and is complete.</p><p><strong>Findings: </strong>Between Sept 1, 2022, and Nov 3, 2023, 24 patients were enrolled and underwent apheresis. Three patients were excluded after apheresis (two patients discontinued due to rapid disease progression and one patient was withdrawn because of failed manufacture of CAR T cells), so 21 patients were infused with anti-BCMA/GPRC5D bispecific CAR T cells. Median follow-up was 5·8 months (IQR 5·2-6·7). Median age was 62 years (IQR 56-67). Eight (38%) patients were male, and 13 (62%) female. All patients were Chinese. At the 4·0 × 10<sup>6</sup> CAR T cells per kg dose, two patients had dose-limiting toxicities, of whom one died of subarachnoid haemorrhage (which was not considered to be related to the study treatment). The maximum tolerated dose was identified as 2·0 × 10<sup>6</sup> CAR T cells per kg. The most common grade 3 or worse adverse events were haematological toxicities in 19 (90%) patients (except lymphopenia). 15 (71%) patients had cytokine release syndrome, of which all cases were grade 1 or 2. One case of grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in a patient who received 4·0 × 10<sup>6</sup> CAR T cells per kg. No ICANS or grade 3 or worse organ toxicities were observed in patients who received 0·5-2·0 × 10<sup>6</sup> CAR T cells per kg. The overall response rate was 86% (18 of 21 patients), with 13 (62%) patients having a complete response or better, and 17 (81%) patients having measurable residual disease negativity. Of the 12 patients who received","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":null,"pages":null},"PeriodicalIF":15.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141767778","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}
Lancet HaematologyPub Date : 2024-10-01Epub Date: 2024-09-20DOI: 10.1016/S2352-3026(24)00270-9
Andrea Linke, Jacqueline Del Castillo, Kirsti Scheffel, Peter Feenstra, Riikka-Leena Manninen
{"title":"Let's talk about sex and haematopoietic stem-cell transplantation.","authors":"Andrea Linke, Jacqueline Del Castillo, Kirsti Scheffel, Peter Feenstra, Riikka-Leena Manninen","doi":"10.1016/S2352-3026(24)00270-9","DOIUrl":"10.1016/S2352-3026(24)00270-9","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":null,"pages":null},"PeriodicalIF":15.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308815","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}
Lancet HaematologyPub Date : 2024-10-01Epub Date: 2024-09-20DOI: 10.1016/S2352-3026(24)00209-6
Tamim Alsuliman, Lugien Alasadi, Alice Polomeni, Antoine Capes, Zinaida Peric, Andrea Linke, Hélène Schoemans, Florent Malard, Yves Chalandon, Mohamad Mohty
{"title":"Sexual health-related psychological and emotional life after allogeneic haematopoietic stem-cell transplantation.","authors":"Tamim Alsuliman, Lugien Alasadi, Alice Polomeni, Antoine Capes, Zinaida Peric, Andrea Linke, Hélène Schoemans, Florent Malard, Yves Chalandon, Mohamad Mohty","doi":"10.1016/S2352-3026(24)00209-6","DOIUrl":"10.1016/S2352-3026(24)00209-6","url":null,"abstract":"<p><p>Sexual health is important for the quality of life of patients who have received haematopoietic stem-cell transplantation (HSCT). Sexual dysfunction and couple dissatisfaction can seriously affect a patient's recovery and treatment process. However, this aspect of post-transplantation recovery is still usually neglected in clinical practice. In this Series paper, we aim to elucidate the emotional and psychosocial factors affecting the sexual function in these patients, with a special focus on the partner's role and the psychological consequences of some adverse effects of HSCT. Moreover, we provide an overview of the management approaches and assessment tools of psychological issues associated with sexual dysfunction reported in the literature. These tools can help clinicians in this field to plan essential lifestyle and clinical interventions to help their patients. In conclusion, screening for psychological issues is indispensable when approaching sexual dysfunction in patients with HSCT. Health-care teams in transplantation units should be trained to discuss this aspect of recovery and provide the required treatment and follow-up plan.</p>","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":null,"pages":null},"PeriodicalIF":15.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308818","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}
Lancet HaematologyPub Date : 2024-10-01Epub Date: 2024-07-24DOI: 10.1016/S2352-3026(24)00148-0
Kwee Yong, Thomas Martin, Meletios-Athanasios Dimopoulos, Joseph Mikhael, Marcelo Capra, Thierry Facon, Roman Hajek, Ivan Špička, Ross Baker, Kihyun Kim, Gracia Martinez, Chang-Ki Min, Ludek Pour, Xavier Leleu, Albert Oriol, Youngil Koh, Kenshi Suzuki, France Casca, Sandrine Macé, Marie-Laure Risse, Philippe Moreau
{"title":"Isatuximab plus carfilzomib-dexamethasone versus carfilzomib-dexamethasone in patients with relapsed multiple myeloma (IKEMA): overall survival analysis of a phase 3, randomised, controlled trial.","authors":"Kwee Yong, Thomas Martin, Meletios-Athanasios Dimopoulos, Joseph Mikhael, Marcelo Capra, Thierry Facon, Roman Hajek, Ivan Špička, Ross Baker, Kihyun Kim, Gracia Martinez, Chang-Ki Min, Ludek Pour, Xavier Leleu, Albert Oriol, Youngil Koh, Kenshi Suzuki, France Casca, Sandrine Macé, Marie-Laure Risse, Philippe Moreau","doi":"10.1016/S2352-3026(24)00148-0","DOIUrl":"10.1016/S2352-3026(24)00148-0","url":null,"abstract":"<p><strong>Background: </strong>Isatuximab is an anti-CD38 monoclonal antibody approved for the treatment of relapsed or refractory multiple myeloma. Previous analyses of the IKEMA trial showed prolonged progression-free survival in patients with this disease who received isatuximab in combination with carfilzomib-dexamethasone as compared with those who received carfilzomib-dexamethasone alone. Herein, we report the analysis of overall survival from the IKEMA trial.</p><p><strong>Methods: </strong>This prospective, randomised, open-label, active-controlled, phase 3 study included patients with relapsed or refractory multiple myeloma aged 18 years or older, who had received one to three previous lines of treatment from 69 study centres in 16 countries across North America, South America, Europe, and the Asia-Pacific region. Patients were randomly allocated (3:2) to treatment with either isatuximab plus carfilzomib-dexamethasone (isatuximab group) or carfilzomib-dexamethasone (control group). In the isatuximab group, patients received intravenous isatuximab (10 mg/kg on days 1, 8, 15, and 22 of the first 28-day cycle, and days 1 and 15 of subsequent 28-day cycles). In both treatment groups, intravenous carfilzomib (20 mg/m<sup>2</sup> on days 1 and 2 of the first cycle; and 56 mg/m<sup>2</sup> on days 8, 9, 15, and 16 of the first cycle, and days 1, 2, 8, 9, 15, and 16 of subsequent cycles) and intravenous or oral dexamethasone (20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23) were administered. The primary endpoint of the trial was progression-free survival, which was reported previously. Treatment continued until progression, unacceptable toxicity, or patient request to discontine. The overall survival analysis reported here was planned to be conducted 3 years after the primary progression-free survival analysis in the intention-to-treat population. Additional analyses were conducted on the secondary endpoints of time to next treatment and second-progression-free survival. Reported p values are non-inferential due to hierarchical testing. This trial is registered with ClinicalTrials.gov (NCT03275285).</p><p><strong>Findings: </strong>Between Nov 15, 2017, and March 21, 2019, 302 patients were enrolled and randomly allocated: 179 (59%) to the isatuximab group and 123 (41%) to the control group. 169 (56%) patients were male, 133 (44%) were female, 214 (71%) were White, 50 (17%) were Asian, nine (3%) were Black or African American, and three (1%) were multiracial. At data cutoff for this overall survival analysis (Feb 7, 2023), 79 (44%) overall survival events in the isatuximab group and 59 (48%) in the control group had occurred (median follow-up 56·61 months [IQR 54·90-58·02]). Median overall survival (in months) was not reached (NR; 95% CI 52·17-NR) in the isatuximab group and was 50·60 months (38·93-NR) in the control group (hazard ratio [HR] 0·855 [95% CI 0·608-1·202], nominal one-sided p=0·18). Survival probability at 48 months was 59·7% (95% CI","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":null,"pages":null},"PeriodicalIF":15.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141789525","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}
Lancet HaematologyPub Date : 2024-10-01Epub Date: 2024-09-20DOI: 10.1016/S2352-3026(24)00244-8
Tamim Alsuliman, Reyes María Martín Rojas, Ahmad Ali Basha, Paolo Musiu, Léonardo Magro, Anna Maria Testi, Mohamad Mohty
{"title":"Sexual health and emotional wellbeing of adolescent and young adult survivors of haematological malignancies.","authors":"Tamim Alsuliman, Reyes María Martín Rojas, Ahmad Ali Basha, Paolo Musiu, Léonardo Magro, Anna Maria Testi, Mohamad Mohty","doi":"10.1016/S2352-3026(24)00244-8","DOIUrl":"10.1016/S2352-3026(24)00244-8","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":null,"pages":null},"PeriodicalIF":15.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308816","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":"Sexual health and emotional wellbeing of patients with haematological malignancies: general review.","authors":"Tamim Alsuliman, Reyes María Martín Rojas, Nour Moukalled, Eolia Brissot, Laurence Quarez-Blaise, Zora Marjanovic, Didier Blaise, Danielle Murphy, Melissa Logue, Bipin N Savani, Mohamad Mohty","doi":"10.1016/S2352-3026(24)00208-4","DOIUrl":"10.1016/S2352-3026(24)00208-4","url":null,"abstract":"<p><p>Sexual health is an important aspect of a person's life. Many patients and haematologists believe that intimacy and sexuality issues are substantial during cancer treatment. The haematological cancer disease, diagnosis, shock of the announcement, treatment, and follow-up appointments, can all have negative effects on the quality of life of patients, their partners, other family members, and friends. Addressing the intimate aspects of patients' lives not only enhances their wellbeing but also contributes to the quality of their survivorship. Progress has been made in the management of sexual life-related complications; however, novel strategies in coordination with a multidisciplinary team need to be implemented. New and comprehensive approaches must be developed on a multidisciplinary scale. In this Series paper, we discuss the factors affecting the sexual life of patients with haematological malignancies, different methods to assess sexual function, as well as management approaches of sexual wellbeing among patients with haematological cancers.</p>","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":null,"pages":null},"PeriodicalIF":15.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308817","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}
Lancet HaematologyPub Date : 2024-10-01Epub Date: 2024-07-23DOI: 10.1016/S2352-3026(24)00205-9
Chenggong Li, Heng Mei
{"title":"Anti-BCMA/GPRC5D bispecific CAR T cells for relapsed or refractory multiple myeloma: is 1 + 1 greater than 2?","authors":"Chenggong Li, Heng Mei","doi":"10.1016/S2352-3026(24)00205-9","DOIUrl":"10.1016/S2352-3026(24)00205-9","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":null,"pages":null},"PeriodicalIF":15.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141767777","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}