British Journal of Haematology最新文献

{"title":"Targeting NLRP1-CCL8 axis in the leukaemic niche suppresses AML via inhibition of PI3K-AKT signalling.","authors":"Xingyue Li, Qi Zhou, Xiaowen Hao, Can Cao, Seyram Yao Adzraku, Xuguang Song, Cai Sun, Xiaofeng Guo, Yue Li, Shengnan Yuan, Yujin Huang, Kailin Xu, Jianlin Qiao, Lingyu Zeng, Wen Ju","doi":"10.1111/bjh.70011","DOIUrl":"https://doi.org/10.1111/bjh.70011","url":null,"abstract":"<p><p>Bone marrow microenvironment not only plays a key role in supporting normal haematopoiesis but also plays an important role in regulating the progression of acute myelogenous leukaemia (AML). Targeting the bone marrow microenvironment will provide new targets for AML treatment. However, until now, the mechanism by which the bone marrow microenvironment promotes AML progression remains obscure. Our previous studies have found that the bone marrow microenvironment Nucleotide-binding Oligomerization Domain (NOD)-Leucine Rich Repeat (LRR)-containing Receptors (NLR) family pyrin domain containing 1 (NLRP1) plays an important role in the regulation of bone marrow endothelial cells, mesenchymal stem cell (MSC) cells and haematopoiesis, but the effect of the bone marrow microenvironment NLRP1 on AML has not been addressed. In this study, we found that niche Nlrp1 KO inhibited AML disease progression and leukaemia stem cell activity. Moreover, Nlrp1 was expressed in the bone marrow microenvironment, especially in MSC. Nlrp1 knockout in MSC inhibits the growth and proliferation of co-cultured leukaemia cells, which is related to Nlrp1 KO inhibition of Ccl8 secretion in MSC and CCL8/CCR1-mediated PI3K-AKT activation in AML cells. Our study highlights the critical role of niche NLRP1 in AML and it could be a therapeutic target for AML.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of secondary hypogammaglobulinaemia in children with acute lymphoblastic leukaemia receiving maintenance chemotherapy.","authors":"Chao-Neng Cheng, Yuan-Ning Yang, Yun-Hsuan Yeh, Jiann-Shiuh Chen","doi":"10.1111/bjh.70027","DOIUrl":"https://doi.org/10.1111/bjh.70027","url":null,"abstract":"<p><p>Hypogammaglobulinaemia is a potential complication in children with acute lymphoblastic leukaemia (ALL) receiving chemotherapy. However, real-world data on its prevalence and clinical impact remain limited. This study retrospectively reviewed 85 paediatric ALL patients completing Taiwan Pediatric Oncology Group (TPOG)-ALL-2013 maintenance therapy to investigate secondary hypogammaglobulinaemia. At diagnosis, 6% (5/85) of patients had hypogammaglobulinaemia, increasing to 49.2% (32/65) during maintenance chemotherapy. Patients with very-high-risk disease, poor cytogenetics or baseline immunoglobulin G (IgG) <1000 mg/dL were more likely to develop secondary hypogammaglobulinaemia. Febrile episodes were significantly more common in the hypogammaglobulinaemia group (40.6% had >10 fever episodes) and were particularly frequent in patients with IgG <400 mg/dL. However, hypogammaglobulinaemia was not associated with white blood cell count, measurable residual disease or long-term survival outcomes. Although intravenous immunoglobulin (IVIG) replacement is well established in primary immunodeficiency and B-cell malignancies, its role in paediatric ALL remains uncertain. Given the high prevalence of hypogammaglobulinaemia and its association with febrile episodes, routine IgG monitoring may help identify at-risk patients. Further studies are needed to determine the clinical benefits of IVIG supplementation in this population.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A predictive serum miRNA signature impacts diffuse large B-cell lymphoma cell viability via inhibition of EGLN1 and TXNRD1 regulators of ferroptosis.","authors":"Giulia Regazzo, Giulia Vari, Francesco Marchesi, Ana Belén Díaz Méndez, Marta Di Giuliani, Andrea Sacconi, Francesca Palombi, Valentina Lulli, Frauke Goeman, Mariangela Novello, Martina Tomassi, Elena Papa, Francesco Bertoni, Stefan Hohaus, Andrea Mengarelli, Maria Giulia Rizzo","doi":"10.1111/bjh.70017","DOIUrl":"https://doi.org/10.1111/bjh.70017","url":null,"abstract":"<p><p>Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disorder. Prognostic factors include genomic alterations and cell-of-origin (COO) subtypes, even though they cannot fully predict treatment response. MicroRNAs (miRNAs) deregulated in patient tumours and blood are promising non-invasive biomarkers. Several circulating miRNAs were found to be correlated with progression-free survival (PFS), independently of other prognosticators. However, miRNA signatures, rather than individual miRNAs, represent more reliable biomarkers and a better mirror of the disease. In this study, we identified circulating miRNAs differentially expressed between R-CHOP refractory and responding subjects by small-RNA sequencing on serum from 33 DLBCL patients. Among the identified miRNAs, the combined expression of three of them improved the predictive performance and was correlated with PFS. Two out of three miRNAs, miR-421 and miR-324-5p, were also differentially expressed in tumour tissues based on treatment response. Overexpressing these miRNAs reduced cell proliferation, viability and resistance to R-CHOP in the germinal centre B-like COO subtype. EGLN1 and TXNRD1, regulators of oxygen metabolism and redox homeostasis, were identified as miRNA targets and the silencing or inhibition of these genes impaired cell viability and induced ferroptosis. These results support the application of a two-miRNA signature and its targets for novel combined therapeutic interventions in DLBCL.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterizing pregnancy outcomes in a humanized mouse model of sickle cell disease.","authors":"Christopher Chambliss, Elizabeth Manci, Earl Fields, Jesse Bueno, Adeola Michael, Elizabeth Eldeiry, Cameron Hall, Beatrice Gee, Satheesh Chonat, David R Archer","doi":"10.1111/bjh.70024","DOIUrl":"https://doi.org/10.1111/bjh.70024","url":null,"abstract":"<p><p>Although increased risk for adverse pregnancy outcomes has been well characterized in women with sickle cell disease (SCD), there remains unexplored value in the characterization of a preclinical model which could minimize human risk. This study aimed to characterize pregnancy outcomes in the SCD mouse model with emphasis on analogous clinical correlates and biological contributors. As such, we identified worsened outcomes including reduced litter sizes (haemoglobin HbSS (SS) 5.18 ± 1.25 embryos vs. haemoglobin HbAA (AA) 6.86 ± 1.51**), fetal weight (SS 0.38 ± 0.16 g vs. AA 0.49 ± 0.14 g**), viability of embryos (SS 20.00% interquartile range (IQR) 33.33 vs. AA 100.00% IQR 0.0***) and maternal mortality (SS 7.14% (2/28) vs. AA 0.00% (0/27) odds ratio (OR) = 4.82 ns). We further noted a significant reduction in vascular density and impaired uterine and umbilical artery blood flow within SCD placentae. Assessments of soluble growth factors revealed evidence of angiogenic dysregulation but maintained limited translational utility due to the multiparous nature of mouse pregnancy. These results serve as a cornerstone characterization of pregnancy outcomes in the SCD mouse model while highlighting the implications of placental vascular insufficiency. They further demonstrate both the utility and limitations of the model, emphasizing the need for continued clinical assessment.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of graft-versus-host disease prophylaxis on second primary malignancies after allogeneic haematopoietic stem cell transplantation.","authors":"Nihar Desai, Eshrak Al-Shaibani, Tommy Alfaro-Moya, Arjun D Law, Wilson Lam, Mats Remberger, Ivan Pasic, Igor Novitzky-Basso, Auro Viswabandya, Dennis D Kim, Rajat Kumar, Jeffrey H Lipton, Jonas Mattsson, Fotios V Michelis","doi":"10.1111/bjh.70006","DOIUrl":"https://doi.org/10.1111/bjh.70006","url":null,"abstract":"<p><p>Second primary malignancies (SPMs) are a well-recognized late complication of allogeneic haematopoietic stem cell transplantation (HSCT). This study aims to evaluate the impact of anti-thymocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy) combination on the incidence of SPMs, compared to other graft-versus-host disease (GvHD) prophylactic regimens. Among 1418 evaluable patients with a median follow-up of 6125 person-years, 138 patients developed an SPM. The cumulative incidence at 5 years was 10.6% (95% CI: 9-13). The use of ATG-PTCy was independently associated with a reduced risk of developing SPM (Hazard Ratio [HR], 0.65; p = 0.02), while older patient age (HR, 1.10; p = 0.03) and moderate-to-severe chronic GvHD (HR, 1.54; p = 0.02) were associated with an increased risk of SPM. Compared to the general population, HSCT recipients were 2.45 times more likely to develop a malignancy (p < 0.01). The 3-year overall survival from the time of SPM diagnosis was 69.8% (95% CI: 61-77) with haematological SPM independently associated with inferior survival (HR: 2.40; 95% CI: 1.3-4.5; p < 0.01). Fifteen patients (11%) developed more than one SPM. In conclusion, ATG-PTCy appears to reduce the risk of SPM post-HSCT. Active surveillance and screening for SPMs in transplant survivors are of paramount importance to ensure favourable outcomes.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into the clinical, platelet and genetic landscape of inherited thrombocytopenia with malignancy risk.","authors":"Ana Marín-Quílez, Ana Sánchez-Fuentes, Ana Zamora-Cánovas, Pedro Luis Gómez-González, Lorena Diaz-Ajenjo, Rocío Benito, Agustín Rodríguez-Alén, Teresa Sevivas, Thais Murciano, Laura Murillo, Nora V Butta, Nuria Revilla, Rosa Campos, Paola Escribano, Jordi Esteve, Nuria Fernández-Mosteirin, Francisca Ferrer-Marín, Laura Hernández, Jorge Huerta-Aragonés, Antonio León, Mónica López-Duarte, Eugenia López, Mónica Martín-Salces, Meritxell Nomdedeu, Raquel Oña, Irene Peláez-Pleguezuelos, Fernando Ramos, Elena Sebastián, Claudia Serrano, Cristina Sierra-Aisa, Rosa Vidal-Laso, José Ramón González-Porras, María Luisa Lozano, José María Bastida, José Rivera","doi":"10.1111/bjh.70001","DOIUrl":"https://doi.org/10.1111/bjh.70001","url":null,"abstract":"<p><p>Inherited thrombocytopenia (IT) with germline variants in RUNX1, ETV6 or ANKRD26 carries a high risk (10%-45%) of developing haematological malignancy (IT-HM). We evaluated the clinical, platelet and molecular characteristics in 37 patients with RUNX1-related thrombocytopenia (RT), 9 with ETV6-RT and 20 with ANRKD26-RT. Genetic diagnosis was delayed by about 20 years from the identification of thrombocytopenia. Bleeding tendency was present in 25%-30% of RUNX1-RT and ANKRD26-RT patients. Platelet aggregation was impaired in 90% of all patients, while reduced activation and granule secretion were heterogeneous. Most RUNX1-RT patients had low glycoprotein Ia (GPIa) levels, which may be a useful disease biomarker. Sixteen distinct genetic variants in RUNX1, four in ETV6 and four in ANKRD26 were identified in patients. The clinical profile showed immune, skin, gastrointestinal and other comorbidities in many patients. One third of the cases developed a malignancy: This included eight RUNX1-RT patients with myelodysplastic syndrome (MDS), five with acute myeloid leukaemia (AML), and one with chronic myeloid leukaemia (CML) Ph+. One patient with ETV6-RT subsequently developed B-cell acute lymphoblastic leukaemia (B-ALL) during childhood. Three cases with ANKRD26-RT demonstrated a multifaceted clinical presentation, including B-ALL Ph+, MDS and breast cancer. The high incidence of HM development highlights the importance of early diagnosis in life.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A win ratio approach for comparing graft-versus-host disease-free, relapse-free survival among alternative donors.","authors":"Yoshimitsu Shimomura, Sho Komukai, Tetsuhisa Kitamura, Kazuki Yoshimura, Yoshihiro Inamoto, Yu Akahoshi, Yachiyo Kuwatsuka, Yoshiaki Usui, Naoyuki Uchida, Masatsugu Tanaka, Makoto Onizuka, Mamiko Sakata-Yanagimoto, Noriko Doki, Yuta Hasegawa, Kazuya Ishiwata, Hirohisa Nakamae, Masashi Sawa, Yuta Katayama, Toshiro Kawakita, Makoto Yoshimitsu, Takahiro Fukuda, Yoshinobu Kanda, Marie Ohbiki, Hideki Nakasone, Junya Kanda","doi":"10.1111/bjh.70008","DOIUrl":"https://doi.org/10.1111/bjh.70008","url":null,"abstract":"<p><p>The optimal alternative donor type for patients lacking human leucocyte antigen (HLA)-matched related or unrelated donors remains unclear. In comparative studies evaluating donor types, graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) represents a well-established end-point but has limitations. The win ratio approach addresses these limitations by analysing multiple end-points with varying severities to account for the relative component priorities. We compared HLA-mismatched unrelated donors, haploidentical donors and cord blood using both the hazard ratio (HR) of GRFS and the win ratio related to GRFS. The haploidentical donor group had a similar HR of GRFS (HR: 1.01, 95% confidence interval [CI]: 0.85-1.19, p = 0.916) and win ratio (win ratio: 0.86, 95% CI: 0.72-1.02, p = 0.081) to HLA-mismatched unrelated donors. Cord blood transplantation showed similar GRFS compared to HLA-mismatched unrelated donors in the Cox proportional model (HR: 1.14, 95% CI: 0.98-1.32, p = 0.085), significantly lower win ratio (win ratio: 0.80, 95% CI: 0.68-0.93, p = 0.004) and similar outcomes to haploidentical donors. HLA-mismatched unrelated donor transplantation showed comparable to superior outcomes among alternative donor types. Our results indicate the need to present the win ratio alongside conventional methods to assess the end-point robustly.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a machine learning-based predictive model for venous thromboembolism risk assessment in orthopaedic patients with routine prophylaxis.","authors":"Chaoyun Yuan, Ruoyu Luo, Jiaqi Li, Yingying Fan, Jiyong Jing","doi":"10.1111/bjh.20265","DOIUrl":"https://doi.org/10.1111/bjh.20265","url":null,"abstract":"<p><p>Despite the use of conventional preventive measures, the long-term risk of the development of venous thromboembolism (VTE) in orthopaedic patients remains high in a high-risk patient population. Accurate risk assessment is critical; however, existing assessment tools appear to have certain limitations, and machine learning (ML) models appear to have higher predictive accuracy. Develop an ML model with clinical features to predict VTE in orthopaedic patients on standard prophylaxis. We used 147 clinical variables with XGBoost and CatBoost models for VTE risk prediction, comparing their performance with the Caprini score. Both internal and external validations were conducted to assess the model's efficacy. SHapley Additive exPlanation (SHAP) values were employed to improve interpretability and accurately evaluate predictive efficacy. Using 8182 patients (153 VTE cases), XGBoost and CatBoost achieved internal Area Under the ROC curves (AUCs) of 0.941 and 0.937. In external validation (2121 patients; 31 VTE cases), AUCs were 0.888 and 0.902. They outperformed traditional methods with high accuracy, balanced sensitivity and specificity. SHAP analysis showed feature importance and VTE correlation across algorithms. This study used two models with clinical features to improve VTE risk prediction accuracy in orthopaedic patients under conventional prevention. The models identified VTE risk factors and highlighted key preventive measures.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of ruxolitinib-based regimen in the treatment of paediatric Epstein-Barr virus-associated haemophagocytic lymphohistiocytosis.","authors":"Wenqian Wang, YunZe Zhao, Jian Ge, Zishi Fang, Chenxin Zhou, Dong Wang, Qing Zhang, Zhigang Li, Tianyou Wang, Rui Zhang","doi":"10.1111/bjh.20264","DOIUrl":"https://doi.org/10.1111/bjh.20264","url":null,"abstract":"<p><p>Ruxolitinib (RUX) has demonstrated efficacy in haemophagocytic lymphohistiocytosis (HLH) patients, but large cohort studies regarding its clinical application in children with Epstein-Barr virus-associated HLH (EBV-HLH) remain scarce. This retrospective study analysed the efficacy and safety of RUX-based regimen (n = 53) and compared it with adjusted HLH-94 chemotherapy (n = 42) in the treatment of paediatric EBV-HLH. The patients treated with the RUX-based regimen received RUX monotherapy as front-line therapy. Additional methylprednisolone and etoposide would be added in sequence if the response was unsatisfactory. At 8 weeks of therapy, the overall response rate of the RUX group was comparable to that of the traditional chemotherapy group (84.9% vs. 76.2%, p = 0.282), with a 12-month survival rate of 92.2% (95% CI: 80.6-97.0) and 87.6% (95% CI: 72.1-94.5) (p = 0.595). In the RUX group, 56.6% of patients achieved sustained remission without requiring etoposide during a median follow-up of 17.2 months. Among these patients, 93.3% had primary EBV infection. The RUX-based regimen was well-tolerated, exhibiting significantly lower incidence of myelosuppression and secondary infection than adjusted HLH-94 chemotherapy (35.8% vs. 95.2%, p < 0.001; 28.3% vs. 59.5%, p = 0.002). Overall, our preliminary results indicated that EBV-HLH children treated with the RUX-based regimen demonstrated favourable efficacy while significantly reducing treatment-related adverse events.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct patient, tumour and chimeric antigen receptor T-cell characteristics are associated with initiating versus sustaining responses to idecabtagene vicleucel in relapsed and refractory multiple myeloma.","authors":"Nathan Martin, Ethan Thompson, Nicholas Stong, Yang Xu, Olivia Finney, Julie Rytlewski, Erin Flynt, Jessica Marfo, Dante B Descalzi-Montoya, Irene Manrique, Bruno Paiva, Nikhil Munshi, Timothy B Campbell, Shari M Kaiser","doi":"10.1111/bjh.70012","DOIUrl":"https://doi.org/10.1111/bjh.70012","url":null,"abstract":"<p><p>Idecabtagene vicleucel (ide-cel), a B-cell maturation antigen (BCMA)-directed autologous chimeric antigen receptor (CAR) T-cell therapy, was studied in relapsed and refractory multiple myeloma after >4 prior lines of therapy in KarMMa (NCT03361748). Translational analyses evaluated patient baseline, tumour and CAR T-cell features associated with initiating and sustaining response to a single ide-cel infusion. Baseline tumour burden, measured by soluble BCMA, and homeostatic cytokine levels released after lymphodepleting chemotherapy were among the top correlates for pharmacodynamic response. Duration of response was associated with tumour genomic features and quality of engraftment indicated by more robust CD4+ CAR T-cell expansion, higher levels of persistent ide-cel and sustained suppression of BCMA-expressing cells. A working model is proposed whereby patient and microenvironment features that may modulate ide-cel activation and expansion influence the probability of response initiation, and that tumour-intrinsic resistance features and sustained engraftment of ide-cel influence the durability of responses.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}