Journal of Hematology & Oncology最新文献

{"title":"Results of a phase 1/2 study of sacituzumab tirumotecan in patients with unresectable locally advanced or metastatic solid tumors refractory to standard therapies","authors":"Quchang Ouyang, Jordi Rodon, Yan Liang, Xinhong Wu, Qun Li, Lihua Song, Min Yan, Zhongsheng Tong, YunPeng Liu, Zev A. Wainberg, Ying Wang, Cuizhi Geng, Susanna V. Ulahannan, Guohua Yu, Manish R. Sharma, Xiang Wang, Judy S. Wang, Alexander Spira, Weihong Zhao, Rachel E. Sanborn, Ying Cheng, Xian Wang, Gesha Liu, Yaling Li, Junyou Ge, Elliot Chartash, Omobolaji O. Akala, Yongmei Yin","doi":"10.1186/s13045-025-01705-2","DOIUrl":"https://doi.org/10.1186/s13045-025-01705-2","url":null,"abstract":"Sacituzumab tirumotecan (sac-TMT) is an antibody–drug conjugate composed of an anti-TROP2 monoclonal antibody coupled to a cytotoxic belotecan-derived topoisomerase I inhibitor (KL610023) via a novel linker. We report results from the phase 1 dose-escalation cohorts in advanced solid tumors and phase 2 expansion cohorts for metastatic triple-negative breast cancer (TNBC) from the first-in-human MK-2870-001 (KL264-01) study (NCT04152499). Patients had unresectable locally advanced/metastatic solid tumors refractory to standard therapies. In the phase 1 dose-escalation cohorts, patients had unresectable locally advanced/metastatic solid tumors refractory to standard therapies. Sac-TMT was administered by intravenous administration every 2 weeks at 2 to 12 mg/kg. In phase 2, patients with TNBC and HR+/HER2− breast cancer received sac-TMT per recommended doses for expansion (RDEs) identified in phase 1. Primary objectives were determining maximum tolerated dose (MTD) of sac-TMT and establishing RDEs (phase 1) and determining ORR per RECIST v1.1 by investigator assessment (phase 2). Adverse events were assessed per NCI-CTCAE version 5.0. Thirty patients were enrolled in phase 1 and received sac-TMT 2 mg/kg (n = 4), 4 mg/kg (n = 7), 5 mg/kg (n = 7), 5.5 mg/kg (n = 5), and 6 mg/kg (n = 7). Five patients had dose-limiting toxicities: grade 3 stomatitis at 4, 5.5, and 6 mg/kg; grade 3 rash at 5 mg/kg; and grade 3 urticaria at 6 mg/kg. MTD was 5.5 mg/kg and RDEs were 4 and 5 mg/kg. In the phase 2 dose expansion, ORR (95% CI) was 34.8% (16.4%, 57.3%) in the 4-mg/kg group (n = 23) and 38.9% (23.1%, 56.5%) in the 5-mg/kg group (n = 36) for TNBC. ORR (95% CI) was 31.7% (18.1%, 48.1%) for HR+/HER2− breast cancer (n = 41). Sac-TMT demonstrated manageable safety profile in patients with unresectable locally advanced/metastatic solid tumors and promising antitumor activity in metastatic TNBC and HR+/HER2 − breast cancer. Sac-TMT is being investigated in phase 3 studies. ClinicalTrials.gov, NCT04152499.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"36 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144228900","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: BCMA/GPRC5D bispecific CAR T-cell therapy for relapsed/refractory multiple myeloma with extramedullary disease: a single-center, single-arm, phase 1 trial","authors":"Hao Yao, Shi-hui Ren, Lin-hui Wang, Ming-qiang Ren, Jiao Cai, Dan Chen, Ying He, Si-han Lai, Bai-tao Dou, Meng-jiao Li, Yan-ling Li, Ya-li Cen, Alex H. Chang, Yi Su, Ling Qiu, Fang-yi Fan","doi":"10.1186/s13045-025-01714-1","DOIUrl":"https://doi.org/10.1186/s13045-025-01714-1","url":null,"abstract":"<p><b>Journal of Hematology & Oncology (2025) 18:56</b></p><p><b>https://doi.org/10.1186/s13045-025-01713-2</b></p><p>The original article has been corrected to restore co-authors Yi Su, Ling Qiu, and Fang-yi Fan (lead contact) to co-Corresponding Authorship which was mistakenly removed by the production team which handled this article.</p><span>Author notes</span><ol><li><p>Hao Yao, Shi-hui Ren, Lin-hui Wang and Ming-qiang Ren contributed equally to this work.</p></li></ol><h3>Authors and Affiliations</h3><ol><li><p>Department of Hematology, Chinese People’s Liberation Army The General Hospital of Western Theater Command, Chengdu, 610083, Sichuan, China</p><p>Hao Yao, Shi-hui Ren, Jiao Cai, Dan Chen, Ying He, Si-han Lai, Bai-tao Dou, Meng-jiao Li, Yan-ling Li, Ya-li Cen, Yi Su, Ling Qiu & Fang-yi Fan</p></li><li><p>Branch of National Clinical Research Center for Hematological Disease, Chengdu, 610083, Sichuan, China</p><p>Hao Yao, Shi-hui Ren, Jiao Cai, Dan Chen, Ying He, Si-han Lai, Bai-tao Dou, Meng-jiao Li, Yan-ling Li, Ya-li Cen, Yi Su, Ling Qiu & Fang-yi Fan</p></li><li><p>Sichuan Clinical Research Center for Hematological Disease, Chengdu, 610083, China</p><p>Hao Yao, Shi-hui Ren, Jiao Cai, Dan Chen, Ying He, Si-han Lai, Bai-tao Dou, Meng-jiao Li, Yan-ling Li, Ya-li Cen, Yi Su, Ling Qiu & Fang-yi Fan</p></li><li><p>Department of Clinical Medicine, North Sichuan Medical College, Nanchong, 637000, Sichuan, China</p><p>Bai-tao Dou, Meng-jiao Li, Yan-ling Li & Fang-yi Fan</p></li><li><p>Institute of Basic Medicine, North Sichuan Medical College, Nanchong, 637000, Sichuan, China</p><p>Hao Yao</p></li><li><p>Department of Hematology, The People’s Hospital of Guizhou Province, Guiyang, 550002, Guizhou, China</p><p>Lin-hui Wang</p></li><li><p>Department of Hematology, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, Guizhou Province, China</p><p>Ming-qiang Ren</p></li><li><p>Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, 200438, China</p><p>Alex H. Chang</p></li><li><p>Shanghai YaKe Biotechnology Ltd., Yangpu District, Shanghai, 200090, China</p><p>Alex H. Chang</p></li></ol><span>Authors</span><ol><li><span>Hao Yao</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Shi-hui Ren</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Lin-hui Wang</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Ming-qiang Ren</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Jiao Cai</span>View author publications<p><span>You can also search for ","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"102 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144211126","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":"Integrated clinical and proteomic-based model for diagnostic and prognostic prediction in pRCC","authors":"Zeya Xu, Linhui Zhang, Jiacheng Lyu, Maoping Cai, Tao Ji, Lin Bai, Liqing Li, Yao Zhu, Huashan Xu, Subei Tan, Hualei Gan, Shujuan Ni, Wenhao Xu, Xi Tian, Aihetaimujiang Anwaier, Beiyan Liu, Qinqin Hou, Guohai Shi, Hailiang Zhang, Jianyuan Zhao, Dingwei Ye, Yuanyuan Qu, Chen Ding","doi":"10.1186/s13045-025-01707-0","DOIUrl":"https://doi.org/10.1186/s13045-025-01707-0","url":null,"abstract":"Papillary renal cell carcinoma (pRCC), a main pathological subtype of non-clear cell RCC (nccRCC), has strong heterogeneity. Comparing to other nccRCC subtypes, advanced pRCC has the poorest prognosis. Due to its lower incidence compared to ccRCC, clinical research and exploration of non-invasive biomarkers for pRCC are limited, and it is often misclassified. Herein, we leveraged the advantages of non-invasive plasma samples and the extensive coverage of mass spectrometry (MS)-based proteomics to develop a series of predictive models. First, we established the RCC subtype diagnostic model, which accurately differentiates pRCC, ccRCC, chromophobe RCC (chRCC), and healthy controls, achieving robust performance with an area under the receiver operating characteristic curve (AUROC) of 0.96 and averaged precision (AP) score of 0.91. Furthermore, recognizing the pivotal role of TNM staging in pRCC clinical management, we developed the the TNM staging diagnostic model with AUROC was 0.92 as the complementary noninvasive strategy. Finally, to facilitate real-time clinical monitoring of progression-free survival (PFS), we integrated routine blood indicators and proteomic features to develop the time-clock progression model, which demonstrated high predictive performance (AUROC > 0.95, AP > 0.95). In summary, this study provides a comprehensive plasma proteomic analysis and establishes diagnostic and prognostic predictive models for pRCC.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"36 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144165414","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":"Panoramic spatial enhanced resolution proteomics (PSERP) reveals tumor architecture and heterogeneity in gliomas","authors":"Ziyan Xu, Yunzhi Wang, Tao Xie, Rongkui Luo, Heng-Li Ni, Hang Xiang, Shaoshuai Tang, Subei Tan, Rundong Fang, Peng Ran, Qiao Zhang, Xiaomeng Xu, Sha Tian, Fuchu He, Wenjun Yang, Chen Ding","doi":"10.1186/s13045-025-01710-5","DOIUrl":"https://doi.org/10.1186/s13045-025-01710-5","url":null,"abstract":"The spatial proteomic profiling of complex tissues is essential for investigating cellular function in physiological and pathological states. However, the imbalance among resolution, protein coverage, and expense precludes their systematic application to analyze whole tissue sections in an unbiased manner and with high resolution. Here, we introduce panoramic spatial enhanced resolution proteomics (PSERP), a method that combines tissue expansion, automated sample segmentation, and tryptic digestion with high-throughput proteomic profiling. The PSERP approach facilitates rapid quantitative profiling of proteomic spatial variability in whole tissue sections at sub-millimeter resolution. We demonstrated the utility of this method for determining the streamlined large-scale spatial proteomic features of gliomas. Specifically, we profiled spatial proteomic features for nine glioma samples across three different mutation types (IDH1-WT/EGFR-mutant, IDH1-mutant, and IDH1/EGFR-double-WT gliomas) at sub-millimeter resolution (corresponding to a total of 2,230 voxels). The results revealed over 10,000 proteins identified in a single slide, which helps us to portray the diverse proteins and pathways with spatial abundance patterns in the context of tumor heterogeneity and cellular features. Our spatial proteomic data revealed distinctive proteomic features of malignant and non-malignant tumor regions and depicted the distribution of proteins from tumor centers to tumor borders and non-malignant tumor regions. Through integrative analysis with single-cell transcriptomic data, we elucidated the cellular composition and cell–cell communications in a spatial context. Our PSERP also includes a spatially resolved tumor-specific peptidome identification workflow that not only enables us to elucidate the spatial expression patterns of tumor-specific peptides in glioma samples with different genomic types but also provides us with opportunities to select combinations of tumor-specific mutational peptides whose expression could cover the maximum tumor regions for future immune therapies. We further demonstrated that combining tumor-specific peptides might enhance the efficacy of immunotherapy in both patient-derived cell (PDC) and patient-derived xenograft (PDX) models. PSERP efficiently retains precise spatial proteomic information within the tissue context and provides a deeper understanding of tissue biology and pathology at the molecular level.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"43 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145880","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":"BCMA/GPRC5D bispecific CAR T-cell therapy for relapsed/refractory multiple myeloma with extramedullary disease: a single-center, single-arm, phase 1 trial.","authors":"Hao Yao,Shi-Hui Ren,Lin-Hui Wang,Ming-Qiang Ren,Jiao Cai,Dan Chen,Ying He,Si-Han Lai,Bai-Tao Dou,Meng-Jiao Li,Yan-Ling Li,Ya-Li Cen,Alex H Chang,Yi Su,Ling Qiu,Fang-Yi Fan","doi":"10.1186/s13045-025-01713-2","DOIUrl":"https://doi.org/10.1186/s13045-025-01713-2","url":null,"abstract":"Relapsed/refractory multiple myeloma (RRMM) with extramedullary disease (EMD) represents a challenging condition, with limited treatment options and poor prognosis. We conducted a phase 1 clinical trial to evaluate the safety and effectiveness of a novel bispecific chimeric antigen receptor (CAR) T-cell therapy targeting two antigens, B-cell maturation antigen and G protein-coupled receptor class C group 5 member D (BCMA/GPRC5D), in this high-risk population. A total of 12 patients were enrolled, of whom 3 were excluded due to disease progression or death before CAR T-cell infusion, despite meeting the inclusion criteria, leaving 9 for analysis. The median follow-up was 6.08 months (Interquartile Range [IQR]: 0.9-16.5). All patients received BCMA/GPRC5D bispecific CAR T-cell therapy after bridging therapy with localized radiotherapy or Elranatamab. Efficacy assessments revealed that 100% of patients achieved partial response (PR) or better, with 44.4% achieving complete response (CR). Common adverse events included hematological toxicities such as anemia, leukopenia, and thrombocytopenia. Cytokine release syndrome (CRS) occurred in 66.7% of patients, all of which were grade 1-2, and no neurotoxicity (ICANS) was observed. The 1-year overall survival (OS) and progression-free survival (PFS) rates were 60% and 63%, respectively. Median OS and PFS were not reached. Collectively, these findings highlight a potential therapeutic strategy involving BCMA/GPRC5D dual-targeted CAR T-cell therapy for patients with aggressive forms of multiple myeloma, particularly those with extramedullary disease, and support the need for further exploration and validation in larger, multi-center clinical studies.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"8 1","pages":"56"},"PeriodicalIF":28.5,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087494","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":"Engineered CRO-CD7 CAR-NK cells derived from pluripotent stem cells avoid fratricide and efficiently suppress human T-cell malignancies","authors":"Yunqing Lin, Ziyun Xiao, Fangxiao Hu, Xiujuan Zheng, Chenyuan Zhang, Yao Wang, Yanhong Liu, Dehao Huang, Zhiqian Wang, Chengxiang Xia, Qitong Weng, Leqiang Zhang, Yaoqin Zhao, Hanmeng Qi, Yiyuan Shen, Yi Chen, Fan Zhang, Jiaxin Wu, Pengcheng Liu, Jiacheng Xu, Lijuan Liu, Yanping Zhu, Jingliao Zhang, Wenbin Qian, Aibin Liang, Xiaofan Zhu, Tongjie Wang, Mengyun Zhang, Jinyong Wang","doi":"10.1186/s13045-025-01712-3","DOIUrl":"https://doi.org/10.1186/s13045-025-01712-3","url":null,"abstract":"T-cell malignancies are highly aggressive hematological tumors with limited effective treatment options. CAR-NK cell therapy targeting CD7 has emerged as a promising approach for treating T-cell malignancies. However, conventional CAR-NK cell therapy faces the challenges of cell fratricide due to CD7 expression on both malignant cells and normal NK cells. Additionally, engineering CARs into human tissue-derived NK cells demonstrates heterogeneity, low transduction efficiency, and high manufacturing costs. The human pluripotent stem cells (hPSCs) were genetically modified by knocking out the CD7 gene and introducing the CD7 CAR expression cassette to generate CD7 KO-CD7 CAR-hPSCs. These modified hPSCs were subsequently differentiated into CD7 KO-CD7 CAR-iNK cells using an efficient organoid induction method. The cytotoxicity of CD7 KO-CD7 CAR-iNK cells against CD7+ tumor cells was evaluated. Furthermore, we overexpressed the CXCR4 gene in CD7 KO-CD7 CAR-hPSCs and derived CXCR4-expressing CD7 KO-CD7 CAR-iNK (CRO-CD7 CAR-iNK) cells. The dynamics of CRO-CD7 CAR-iNK cells in vivo were tracked, and their therapeutic efficacy was assessed using human T-cell acute lymphoblastic leukemia (T-ALL) xenograft models. The CD7 KO-CD7 CAR-iNK cells derived from CD7 KO-CD7 CAR-hPSCs effectively avoided fratricide, demonstrated normal expansion, and exhibited potent and specific anti-tumor activity against CD7+ T-cell tumor cell lines and primary T-ALL cells. CXCR4 overexpression in CRO-CD7 CAR-iNK cells improved their homing capacity and extended their persistence in vivo. The CRO-CD7 CAR-iNK cells significantly suppressed tumor growth and prolonged the survival of T-ALL tumor-bearing mice. Our study provides a reliable strategy for the large-scale generation of fratricide-resistant CD7 CAR-iNK cells with robust anti-tumor effects from hPSCs, offering a promising cell product to treat T-cell malignancies.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"230 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097333","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":"Molecular characterization and predictors of relapse in patients with Ph + ALL after frontline ponatinib and blinatumomab","authors":"Nicholas J. Short, Hagop Kantarjian, Ken Furudate, Nitin Jain, Farhad Ravandi, Omer Karrar, Sanam Loghavi, Lewis Nasr, Fadi G. Haddad, Jayastu Senapati, Rebecca Garris, Koichi Takahashi, Elias Jabbour","doi":"10.1186/s13045-025-01709-y","DOIUrl":"https://doi.org/10.1186/s13045-025-01709-y","url":null,"abstract":"Several studies have suggested that chemotherapy-free regimens consisting of blinatumomab and a BCR::ABL1 tyrosine kinase inhibitor are highly effective in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). However, the clinical and molecular characteristics that predict for relapse with these chemotherapy-free regimens are largely unknown. We conducted a prospective phase II clinical trial of the combination of blinatumomab and ponatinib in 76 patients with newly diagnosed Ph + ALL. Patients received 12–15 doses of intrathecal chemotherapy as central nervous systemic (CNS) prophylaxis. The patterns of relapse and the clinical and molecular predictors of relapse were analyzed. With a median follow-up of 29 months, the estimated 3-year event-free survival rate was 78% and the 3-year overall survival rate was 88%. Ten patients (13%) relapsed, with a median time to relapse of 18 months (range, 8–24 months). Six relapses occurred only in extramedullary sites (CNS, n = 5; peritoneum and lymph nodes, n = 1). CD19 expression remained high at relapse in all patients. On univariate analysis, factors associated with an increased risk of relapse were: white blood cell (WBC) ≥ 70 × 109/L at diagnosis (sHR 8.86 [95% CI 2.33–33.70]; P = 0.001), CNS involvement at diagnosis (sHR 6.87 [95% CI 1.54–30.68]; P = 0.01), and VPREB1 deletion (sHR 4.06 [95% CI 1.05–15.76]; P = 0.04). WBC ≥ 70 × 109/L was present in 22% of the cohort and was associated with a 53% cumulative incidence of relapse (CIR), as compared with a CIR rate of 6% for patients with WBC < 70 × 109/L. Neither IKZF1plus genotype, BCR::ABL1 transcript type, nor measurable residual disease kinetics by next-generation sequencing for IG/TR rearrangements significantly impacted the risk of relapse. High WBC at diagnosis was the only variable significantly associated with relapse on multivariate analysis (sHR 16.29 [95% CI 2.35–113.00; P = 0.005). WBC ≥ 70 × 109/L is a high-risk feature in patients with Ph + ALL receiving frontline blinatumomab and ponatinib and may supersede the prognostic importance of baseline molecular features. Alternative frontline treatment strategies may be needed for these patients to reduce the risk of relapse and improve long-term outcomes. ClinicalTrials.gov (NCT03263572).","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"122 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979406","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":"Practice-changing updates on multiple myeloma: highlights from the 2024 ASH annual meeting","authors":"Ioannis Ntanasis-Stathopoulos, Panagiotis Malandrakis, Maria Gavriatopoulou","doi":"10.1186/s13045-025-01711-4","DOIUrl":"https://doi.org/10.1186/s13045-025-01711-4","url":null,"abstract":"Although multiple myeloma (MM) remains an incurable disease, the advancements in patient management are rapid and novel approaches emerge each year. At the last congress of the American Society of Hematology (ASH) 2024, several practice-changing studies were presented that challenge current standards of care for patients with multiple myeloma. The AQUILA study introduced monotherapy with daratumumab for patients with high-risk smoldering MM. For both transplant eligible and ineligible patients with symptomatic MM, anti-CD38-based quadruplets are now established as the primary standard regimens. Emerging data has demonstrated the utility of belantamab mafodotin, an anti-BCMA antibody drug conjugate, in combination with other standard therapies in early relapsed myeloma. Furthermore, a more simplified myeloma response assessment may be feasible. Overall, we provide a critical summary of key studies on MM from the last ASH meeting.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"123 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939704","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":"CD19 CAR-T in relapsed t(8;21) AML: a single-center prospective phase II clinical trial.","authors":"Jia Yin,Qing-Ya Cui,Hai-Ping Dai,Chang-Ju Qu,Zheng Li,Li-Qing Kang,Wei Cui,Xiao-Peng Tian,Xia-Ming Zhu,Lei Yu,De-Pei Wu,Xiao-Wen Tang","doi":"10.1186/s13045-025-01708-z","DOIUrl":"https://doi.org/10.1186/s13045-025-01708-z","url":null,"abstract":"Approximately 78.3% of patients with t(8;21) acute myeloid leukemia (AML) express CD19, making it a potential target for chimeric antigen receptor (CAR)-T cell therapy focused on CD19. This prospective phase II trial (NCT03896854) evaluated the safety and efficacy of CD19 CAR-T cell treatment in 10 relapsed CD19-positive t(8;21) AML patients. This study enrolled eight patients with hematologic and two with molecular relapsed AML. The median bone marrow blast percentage was 12.4% (0.1-50.2%), and the blasts exhibited a median CD19 positivity of 55.7% (22.6-97.1%). Genetic profiling revealed TP53 alterations (n = 1), KIT (n = 3) and FLT3-ITD (n = 1) mutations. After lymphodepletion with fludarabine and cyclophosphamide (FC), 5-20 × 106 cells per kilogram of CAR-T cells were administered. All patients experienced grade 3 or higher hematologic toxicities following tumor-reduction chemotherapy and the FC regimen, which were managed for a median of two weeks after CAR-T treatment. Non-hematological toxicities were mild and reversible. Eight patients presented with mild (grade 1-2) cytokine release syndrome (CRS), and one experienced grade 3 CRS. The immune effector cell-associated neurotoxicity syndrome was not observed. All patients achieved complete remission (CR) after CAR-T, with 60% achieving a molecularly MRD-negative CR. RUNX1::RUNX1T1 fusion transcript levels demonstrated a median 2.5-log reduction (range: 0.7-4.5 log; P = 0.002). At a median follow-up of 64.6 months (range: 11.2-88.8 months), the median overall survival and leukemia-free survival were 11.6 and 3.8 months, respectively. The 12-month cumulative incidence of relapse was 53.3%. These findings indicated that CD19 CAR-T was a safe and effective option for relapsed CD19-positive t(8;21) AML.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"16 1","pages":"53"},"PeriodicalIF":28.5,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915089","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":"Targeted degradation of extracellular proteins: state of the art and diversity of degrader designs","authors":"M. A. A. Mamun, Anush G. Bakunts, Alexander L. Chernorudskiy","doi":"10.1186/s13045-025-01703-4","DOIUrl":"https://doi.org/10.1186/s13045-025-01703-4","url":null,"abstract":"Selective elimination of proteins associated with the pathogenesis of diseases is an emerging therapeutic modality with distinct advantages over traditional inhibitor-based approaches. This strategy, called targeted protein degradation (TPD), is based on hijacking the cellular proteolytic machinery using chimeric degrader molecules that physically link the target protein of interest with the degradation effectors. The TPD era began with the development of PROteolysis TAtrgeting Chimeras (PROTACs) in 2001, with various methods and applications currently available. Classical PROTAC molecules are heterobifunctional chimeras linking target proteins with E3 ubiquitin ligases. This induced interaction leads to the ubiquitylation of the target protein, which is needed for its recognition and subsequent degradation by the cellular proteasomes. However, this technology is limited to intracellular proteins since the effectors involved (E3 ubiquitin ligases and proteasomes) are located in the cytosol. The related methods for selective destruction of proteins present in the extracellular space have only emerged recently and are collectively termed extracellular TPD (eTPD). The prototypic eTPD technology utilizes LYsosomal TArgeting Chimeras (LYTACs) that link extracellular target proteins (secreted or membrane-associated) to lysosome-targeting receptors (LTRs) on the cell surface. The resulting complex is then internalized by endocytosis and trafficked to lysosomes, where the target protein is degraded. The successful elimination of various extracellular proteins via LYTACs and related approaches has been reported, including several important targets in oncology that drive tumor growth and dissemination. This review summarizes current progress in the eTPD field and focuses primarily on the respective technological developments. It discusses the design principles and diversity of degrader molecules and the landscape of available targets and effectors that can be employed for eTPD. Finally, it emphasizes current open questions, challenges, and perspectives of this technological platform to promote the expansion of the eTPD toolkit and further development of its therapeutic applications.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"72 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893130","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}