Journal of Hematology & Oncology最新文献

{"title":"In vivo gene editing and in situ generation of chimeric antigen receptor cells for next-generation cancer immunotherapy","authors":"Weiyue Zhang, Xin Huang","doi":"10.1186/s13045-024-01633-7","DOIUrl":"https://doi.org/10.1186/s13045-024-01633-7","url":null,"abstract":"Chimeric antigen receptor (CAR) cell therapy has achieved groundbreaking success in treating hematological malignancies. However, its application to solid tumors remains challenging due to complex manufacturing processes, limited in vivo persistence, and transient therapeutic effects. In vivo CAR-immune cells induced by gene delivery systems loaded with CAR genes and gene-editing tools have shown efficiency for anti-tumor immunotherapy. In situ programming of autologous immune cells avoids the safety concerns of allogeneic immune cells, and the manufacture of gene delivery systems could be standardized. Therefore, the in vivo editing and in situ generation of CAR-immune cells might potentially overcome the abovementioned limitations of current CAR cell therapy. This review mainly focuses on CAR structures, gene-editing tools, and gene delivery techniques applied in anti-tumor immunotherapy to help design and develop in situ CAR-immune cell therapy. The recent applications of in vivo CAR-immune cell therapy in both hematologic malignancies and solid tumors are investigated. To sum up, the in vivo editing and in situ generation of CAR therapy holds promise for offering a practical, cost-effective, efficient, safe, and widely applicable approach to the next-generation anti-tumor immunotherapy.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"63 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601200","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":"Iparomlimab (QL1604) in patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) unresectable or metastatic solid tumors: a pivotal, single-arm, multicenter, phase II trial","authors":"Feng Bi, Jian Dong, Chuan Jin, Zuoxing Niu, Wenhui Yang, Yifu He, Dajun Yu, Meili Sun, Teng Wang, Xianli Yin, Ruixing Zhang, Kehe Chen, Keming Wang, Zhiwu Wang, Wei Li, Zhongtao Zhang, Hangyu Zhang, Qunyi Guo, Xin Wang, Lei Han, Xizhi Zhang, Wei Shen, Liangming Zhang, Jieer Ying, Miao Wu, Weiguo Hu, Zeng Li, Xiaofen Li, Wenlei Feng, Baihui Zhang, Lingyan Li, Xiaoyan Kang, Weijian Guo","doi":"10.1186/s13045-024-01627-5","DOIUrl":"https://doi.org/10.1186/s13045-024-01627-5","url":null,"abstract":"Though several anti-PD-1/PD-L1 antibodies approved for monotherapy in microsatellite instability-high or mismatch repair-deficient unresectable/metastatic solid tumors, novel immunotherapy with better anti-tumor activity is needed in clinic. In this single-arm, multicenter, pivotal, phase II study, patients received iparomlimab (a novel humanized anti-PD-1 mAb, 200 mg or 3 mg/kg for patients with body weight < 40 kg, IV, Q3W) until disease progression, intolerable toxicities, withdrawal of consent, death, or up to 2 years. The primary endpoint was objective response rate (ORR) assessed by independent radiological review committee (IRRC). Totally, 120 patients were enrolled, of whom 60 patients failed from prior standard therapy, were enrolled in the full analysis set (FAS). As of Jan 20, 2024, the confirmed ORR per IRRC in FAS were 50.0% (30/60; 95% CI 36.8–63.2%) patients, including 4 (6.7%) complete response (CR) and 26 (43.3%) partial response (PR). In colorectal cancer (CRC) patients in FAS, the ORR reached 57.9% (22/38; 95% CI 40.8–73.7%) per IRRC, with 3 (7.9%) CR and 19 (50.0%) PR. Furtherly, the ORRs in liver metastatic or non-liver metastatic CRC patients were 52.9% (9/17, 95% CI 27.8–77.0%) vs 61.9% (13/21, 95% CI 38.4%–81.9%). The incidence of TRAE was 90.8% (any grade) and 20.8% (grade ≥ 3). Immune-related adverse events occurred in 33.3% (any grade) and 5.0% (grade ≥ 3) of patients. No iparomlimab-related death occurred. Iparomlimab presented encouraging antitumor activity with durable response and tolerable safety profile. Trial registration ClinicalTrials.gov Identifier: NCT04326829.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"4 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142598315","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":"RAS signaling in carcinogenesis, cancer therapy and resistance mechanisms","authors":"Xiaojuan Yang, Hong Wu","doi":"10.1186/s13045-024-01631-9","DOIUrl":"https://doi.org/10.1186/s13045-024-01631-9","url":null,"abstract":"Variants in the RAS family (HRAS, NRAS and KRAS) are among the most common mutations found in cancer. About 19% patients with cancer harbor RAS mutations, which are typically associated with poor clinical outcomes. Over the past four decades, KRAS has long been considered an undruggable target due to the absence of suitable small-molecule binding sites within its mutant isoforms. However, recent advancements in drug design have made RAS-targeting therapies viable, particularly with the approval of direct KRASG12C inhibitors, such as sotorasib and adagrasib, for treating non-small cell lung cancer (NSCLC) with KRASG12C mutations. Other KRAS-mutant inhibitors targeting KRASG12D are currently being developed for use in the clinic, particularly for treating highly refractory malignancies like pancreatic cancer. Herein, we provide an overview of RAS signaling, further detailing the roles of the RAS signaling pathway in carcinogenesis. This includes a summary of RAS mutations in human cancers and an emphasis on therapeutic approaches, as well as de novo, acquired, and adaptive resistance in various malignancies.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"2 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596945","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":"A single-cell transcriptomic map of the murine and human multiple myeloma immune microenvironment across disease stages","authors":"Emma Verheye, Daliya Kancheva, Hatice Satilmis, Niels Vandewalle, Rong Fan, Pauline M. R. Bardet, Emile J. Clappaert, Kevin Verstaen, Ann De Becker, Karin Vanderkerken, Kim De Veirman, Damya Laoui","doi":"10.1186/s13045-024-01629-3","DOIUrl":"https://doi.org/10.1186/s13045-024-01629-3","url":null,"abstract":"The long-term effectiveness of immunotherapies against Multiple Myeloma (MM) remains elusive, demonstrated by the inevitable relapse in patients. This underscores the urgent need for an in-depth analysis of the MM tumor-immune microenvironment (TME). Hereto, a representative immunocompetent MM mouse model can offer a valuable approach to study the dynamic changes within the MM-TME and to uncover potential resistance mechanisms hampering effective and durable therapeutic strategies in MM. We generated a comprehensive single-cell RNA-sequencing atlas of the MM-TME in bone marrow and spleen encompassing different stages of disease, using the immunocompetent 5T33MM mouse model. Through comparative analysis, we correlated our murine dataset with the pathogenesis in MM patients by reanalyzing publicly available datasets of human bone marrow samples across various disease stages. Using flow cytometry, we validated the dynamic changes upon disease progression in the 5T33MM model. Furthermore, interesting target populations, as well as the immune-boosting anti-CD40 agonist (αCD40) therapy were tested ex vivo on murine and human primary samples and in vivo using the 5T33MM model. In this study, we identified the heterogenous and dynamic changes within the TME of murine and human MM. We found that the MM-TME was characterized by an increase in T cells, accompanied with an exhausted phenotype. Although neutrophils appeared to be rather innocuous at early disease stages, they acquired a pro-tumorigenic phenotype during MM progression. Moreover, conventional dendritic cells (cDCs) showed a less activated phenotype in MM, underscoring the potential of immune-boosting therapies such as αCD40 therapy. Importantly, we provided the first pre-clinical evaluation of αCD40 therapy and demonstrated successful induction of cDC- and T-cell activation, accompanied by a significant short-term anti-tumor response. This resource provides a comprehensive and detailed immune atlas of the evolution in human and murine MM disease progression. Our findings can contribute to immune-based patient stratification and facilitate the development of novel and durable (immune) therapeutic strategies in MM.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"8 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596976","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":"Hemophagocytic lymphohistiocytosis: current treatment advances, emerging targeted therapy and underlying mechanisms","authors":"Yijun Wu, Xu Sun, Kai Kang, Yuqi Yang, He Li, Ailin Zhao, Ting Niu","doi":"10.1186/s13045-024-01621-x","DOIUrl":"https://doi.org/10.1186/s13045-024-01621-x","url":null,"abstract":"Hemophagocytic lymphohistiocytosis (HLH) is a rapidly progressing, life-threatening syndrome characterized by excessive immune activation, often presenting as a complex cytokine storm. This hyperactive immune response can lead to multi-organ failure and systemic damage, resulting in an extremely short survival period if left untreated. Over the past decades, although HLH has garnered increasing attention from researchers, there have been few advancements in its treatment. The cytokine storm plays a crucial role in the treatment of HLH. Investigating the detailed mechanisms behind cytokine storms offers insights into targeted therapeutic approaches, potentially aiding in early intervention and improving the clinical outcome of HLH patients. To date, there is only one targeted therapy, emapalumab targeting interferon-γ, that has gained approval for primary HLH. This review aims to summarize the current treatment advances, emerging targeted therapeutics and underlying mechanisms of HLH, highlighting its newly discovered targets potentially involved in cytokine storms, which are expected to drive the development of novel treatments and offer fresh perspectives for future studies. Besides, multi-targeted combination therapy may be essential for disease control, but further trials are required to determine the optimal treatment mode for HLH.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"94 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594813","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":"Optimizing CAR-T cell therapy for solid tumors: current challenges and potential strategies","authors":"Kexin Ai, Bowen Liu, Xiaomei Chen, Chuxin Huang, liping Yang, Weiya Zhang, Jianyu Weng, Xin Du, Kongming Wu, Peilong Lai","doi":"10.1186/s13045-024-01625-7","DOIUrl":"https://doi.org/10.1186/s13045-024-01625-7","url":null,"abstract":"Chimeric antigen receptor (CAR)-T cell therapy demonstrates substantial efficacy in various hematological malignancies. However, its application in solid tumors is still limited. Clinical studies report suboptimal outcomes such as reduced cytotoxicity of CAR-T cells and tumor evasion, underscoring the need to address the challenges of sliding cytotoxicity in CAR-T cells. Despite improvements from fourth and next-generation CAR-T cells, new challenges include systemic toxicity from continuously secreted proteins, low productivity, and elevated costs. Recent research targets genetic modifications to boost killing potential, metabolic interventions to hinder tumor progression, and diverse combination strategies to enhance CAR-T cell therapy. Efforts to reduce the duration and cost of CAR-T cell therapy include developing allogenic and in-vivo approaches, promising significant future advancements. Concurrently, innovative technologies and platforms enhance the potential of CAR-T cell therapy to overcome limitations in treating solid tumors. This review explores strategies to optimize CAR-T cell therapies for solid tumors, focusing on enhancing cytotoxicity and overcoming application restrictions. We summarize recent advances in T cell subset selection, CAR-T structural modifications, infiltration enhancement, genetic and metabolic interventions, production optimization, and the integration of novel technologies, presenting therapeutic approaches that could improve CAR-T cell therapy’s efficacy and applicability in solid tumors.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"7 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580062","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":"Prognostic impact of donor mitochondrial genomic variants in myelodysplastic neoplasms after stem-cell transplantation","authors":"Jing Dong, Shahram Arsang-Jang, Tao Zhang, Zhongyuan Chen, Yung-Tsi Bolon, Stephen Spellman, Raul Urrutia, Paul Auer, Wael Saber","doi":"10.1186/s13045-024-01622-w","DOIUrl":"https://doi.org/10.1186/s13045-024-01622-w","url":null,"abstract":"Mitochondrial DNA (mtDNA) variants in patients with myelodysplastic neoplasms (MDS) are shown to be prognostic of outcomes after allogeneic hematopoietic cell transplantation (allo-HCT). However, the prognostic impact of donor mtDNA variants is unknown. Here, we performed whole-genome sequencing on 494 donors who were matched to MDS patients enrolled in the Center for International Blood and Marrow Transplant Research (CIBMTR). We evaluated the impact of donor mtDNA variants on recipients’ transplantation outcomes, including overall survival, relapse, relapse-free survival, and transplant-related mortality. The optimism-adjusted bootstrap method was employed to evaluate the prognostic performance of models that include donor mtDNA variants alone and combined with MDS- and HCT-related clinical factors. In the entire donor cohort, we identified 1,825 mtDNA variants, including 67 potential pathogenic variants. Genetic variants on MT-CYB and MT-ND5 genes were identified as independent predictors of posttransplant outcomes. Integration of donor mtDNA variants into the models based on the International Prognostic Scoring System-Revised (IPSS-R) could capture more prognostic information for MDS patients. Sensitivity analysis in 397 unrelated donors obtained similar results. More importantly, we found that incorporating donor mtDNA variants with donor age and the degree of HLA-matching could help to identify “suboptimal” younger HLA-well-matched unrelated donors and “optimal” older HLA-partially/mismatched unrelated donors. Our study shows that mtDNA variants in donors, including those from unrelated donors, hold prognostic value for MDS patients undergoing allo-HCT and augment the prognostic stratification of current scoring systems. These findings present an opportunity to refine donor selection strategies and improve posttransplant outcomes for MDS patients.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"48 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574374","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":"Long-term survival with donor CD19 CAR-T cell treatment for relapsed patients after allogeneic hematopietic stem cell transplantation.","authors":"Cheng Zhang, Xiaoqi Wang, Hai Yi, Yi Wang, Zhiling Yan, Jian Zhou, Ting Yang, Aibin Liang, Zhen Wang, Yingying Ma, Qin Wen, Lei Gao, Li Gao, Peiyan Kong, Xu Tan, Erlie Jiang, Xi Zhang","doi":"10.1186/s13045-024-01626-6","DOIUrl":"10.1186/s13045-024-01626-6","url":null,"abstract":"<p><p>Chimeric Antigen Receptor T (CAR-T) cell therapy has significantly advanced in treating B-cell acute lymphoblastic leukemia (B-ALL) and has shown efficacy in managing relapsed B-ALL after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Donor-derived CAR-T cell offer both high efficacy and rapid response. Although promising results exist, current research lacks definitive evidence of long-term survival benefits for patients treated with donor-derived CAR-T therapy. We report the long-term survival of 32 patients with post-transplant relapsed B-ALL treated with donor-derived CD19 CAR-T cell, achieving either complete Remission (CR) or CR with incomplete peripheral blood recovery (CRi). The median follow-up was 42 months, with 2-year overall survival (OS) and event-free survival (EFS) rates of 56.25% and 50.0%, respectively. The 5-year OS and EFS rates were 53.13% and 46.88%, with no new long-term adverse events observed. These findings demonstrate good long-term safety, supporting donor-derived CAR-T cell as a recommended treatment option for relapsed B-ALL patients post-transplantation. Trial registration: https://www.chictr.org.cn/showproj.html?proj=14315 . Registration number: ChiCTR-OOC-16008447.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"17 1","pages":"103"},"PeriodicalIF":29.5,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of the post-CAR prognostic index for large B-cell lymphoma patients after CAR-T progression in third or later line treatment.","authors":"Gloria Iacoboni, Víctor Navarro, Pierre Sesques, Kai Rejeski, Mariana Bastos-Oreiro, Fabio Serpenti, Ana Africa Martin Lopez, Josu Iraola-Truchuelo, Javier Delgado, Ariadna Perez, Manuel Guerreiro, Ana Carolina Caballero, Nuria Martinez-Cibrian, Hugo Luzardo Henriquez, Jose Maria Sanchez Pina, Juan-Manuel Sancho, Hervé Ghesquieres, Alberto Mussetti, Lucia Lopez Corral, Rafael Hernani, Juan Luis Reguera, Anna Sureda, Francesc Bosch, Alejandro Martin Garcia-Sancho, Mi Kwon, Marion Subklewe, Andrea Kuhnl, Emmanuel Bachy, Pere Barba, Guillermo Villacampa, Pau Abrisqueta","doi":"10.1186/s13045-024-01608-8","DOIUrl":"10.1186/s13045-024-01608-8","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T-cell therapy fails to achieve durable responses in over 60% of relapsed/refractory (R/R) large B-cell lymphoma (LBCL) patients in the third or later line setting. After CAR-T failure, survival outcomes are heterogeneous and a prognostic model in this patient population is lacking. A training cohort of 216 patients with progressive disease (PD) after CAR-T from 12 Spanish centers was used to develop the Post-CAR Prognostic Index (PC-PI); primary endpoint was overall survival (OS) from CAR-T progression. Validation was performed in an external cohort from three different European centers (n = 204). The prognostic score incorporated five variables, assessed at time of PD to CAR-T: ECOG (> 0), hemoglobin (< 10 g/dL), LDH (≥ 2xULN), number of extranodal sites (> 1) and time from CAR-T to PD (< 4 months). Patients were classified in four risk groups with distinct OS (p-value < 0.05 in all comparisons). In the validation cohort, median OS in the low (31%), intermediate-low (26%), intermediate-high (17%) and high risk (26%) were 15.7, 7.1, 1.8 and 1.0 months, respectively (p < 0.05 in all comparisons). Results were consistent following adjustment for subsequent treatment. In the external cohort, the PC-PI showed a C-statistic of 0.79 (95%CI 0.76-0.82), outperforming IPI and R-IPI. In conclusion, the PC-PI score is a novel tool for OS prediction and could facilitate risk-adapted management of LBCL patients relapsing after CAR T-cells. Additionally, these results will help stratification and interpretation of trials and real-world data incorporating CART-exposed patients.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"17 1","pages":"102"},"PeriodicalIF":29.5,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tucidinostat plus pediatric-inspired chemotherapy for newly diagnosed adult ETP-ALL/LBL: a single-arm, phase 2 trial","authors":"Jieping Lin, Zicong Huang, Zihong Cai, Jia Li, Zhen Li, Chenhao Ding, Zhixiang Wang, Xiaofang Li, Xuan Zhou, Bailin He, Wenhao Zhong, Li Xuan, Qifa Liu, Yang Xu, Hongsheng Zhou","doi":"10.1186/s13045-024-01624-8","DOIUrl":"https://doi.org/10.1186/s13045-024-01624-8","url":null,"abstract":"Early T-cell precursor lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) is a distinct subtype of T-ALL/LBL, characterized by a poor response to initial chemotherapy, a high relapse rate, and an inferior outcome. The treatment options for ETP-ALL/LBL are currently limited, and there are no reported clinical trials available for ETP-ALL/LBL. From June 2018 to June 2022, we conducted a single-arm, single-center, phase 2 trial (NCT03553238) in newly diagnosed ETP-ALL/LBL (age 14–55). Patients (N = 54) received pediatric-inspired chemotherapy plus tucidinostat, which was orally administered once daily at a dosage of 10 mg from induction to consolidation therapy. The primary endpoint was 3 year event-free survival (EFS). Secondary endpoints were overall survival (OS), relapse-free survival (RFS), complete remission rate and adverse events. The composite complete remission (CRc, complete response [CR] plus complete response with incomplete blood count recovery [CRi]) rate and MRD negativity after induction therapy was 91% (49 of 54 patients) and 65% (35 of 54 patients), respectively. The MRD negativity after consolidation was achieved in 87% patients (47 of 54 patients). With a median follow-up of 39.3 months (IQR, 20.6 to 60.0), the 3 year EFS rate was 67.7% (95% CI 56.2–81.7), the 3 year OS rate was 71.5% (95% CI 60.2–84.9) and the 3 year RFS rate was 67.5% (95% CI 55.9–81.6). The most common grade 3–4 adverse events were neutropenia (94%), anemia (85%), thrombocytopenia (76%), and infection (53%). Tucidinostat plus pediatric regimen is an effective and well-tolerated regimen for new diagnosed ETP-ALL/LBL, with high CRc and MRD negativity rates, as well as encouraging survival outcomes.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"75 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519316","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}