Journal of Hematology & Oncology最新文献

{"title":"A first-in-class bifunctional antibody targeting CD20 and CD37 remodels the immune microenvironment in relapsed or refractory B-cell malignancies.","authors":"Li Wang, Jiaying Liu, Keshu Zhou, Zengjun Li, Yun Zeng, Ying Qian, Yuping Sun, Hui Wu, Lindsay Roerker, Peter Tan, Chen Ma, Liwei Zhou, Xianlin Duan, Xiaoyan Kang, Wei-Li Zhao","doi":"10.1186/s13045-026-01796-5","DOIUrl":"10.1186/s13045-026-01796-5","url":null,"abstract":"<p><strong>Background: </strong>Bispecific antibodies engaging CD3 have transformed the treatment landscape of B-cell malignancies but remain constrained by T-cell overactivation and cytokine release. Here, we describe PSB202, a first-in-class bifunctional antibody co-targeting CD20 and CD37 to deplete malignant B cells independently of T-cell engagement.</p><p><strong>Methods: </strong>In this multicenter, open-label phase Ia trial (NCT05003141), adults with relapsed or refractory (R/R) CD20⁺ B-cell non-Hodgkin lymphoma (B-NHL) received escalating doses of PSB202 from 12 to 300 mg. Primary endpoints were dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD). Secondary endpoints were safety, pharmacokinetics, pharmacodynamics, and efficacy.</p><p><strong>Results: </strong>Fifteen heavily-pretreated patients were enrolled, with a median age of 67.7 years (range, 54-78). One DLT of grade 4 neutropenia occurred at 100 mg. MTD was not reached. PSB202 showed a manageable safety profile, with grade ≥ 3 neutropenia and leukopenia both occurring in 60% of patients. The overall response rate was 30% in 10 evaluable patients, including one complete response at 300 mg. PSB202 achieved sustained B-cell depletion and induced IFN-γ release without cytokine release syndrome. Single-cell sequencing revealed different immune microenvironments in responders and non-responders, and the treatment also induced alterations.</p><p><strong>Conclusions: </strong>PSB202 may represent a novel dual-targeting strategy that possibly mitigates CD3-related toxicity while promoting cytotoxic immune activation. These findings support further clinical development of PSB202 as an off-the-shelf therapeutic alternative for R/R B-NHL.</p><p><strong>Trial registration: </strong>This study was registered with ClinicalTrials.gov, NCT05003141.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":" ","pages":""},"PeriodicalIF":47.8,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13231790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054973","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":"Cardiovascular adverse events associated with bispecific antibodies in relapsed or refractory B-cell non-Hodgkin lymphomas.","authors":"Malak Munir, Ahmed Sayed, Dae Hyun Lee, Farrukh Awan, Sanam Ghazi, Jean Kim, Daniel Addison, Narendranath Epperla","doi":"10.1186/s13045-026-01809-3","DOIUrl":"10.1186/s13045-026-01809-3","url":null,"abstract":"<p><p>Bispecific antibodies (BsAb) approved for relapsed/refractory B-cell non-Hodgkin lymphomas (R/R NHL) redirect T-cells to malignant cells and have been associated with cardiovascular adverse events (CVAEs). We analyzed the FDA Adverse Event Reporting System (FAERS) data from December 2022 to September 2025 to characterize the safety of mosunetuzumab, glofitamab, and epcoritamab. Among 246,490 adverse event reports, 1,931 involved BsAbs. CVAEs occurred in 336 (17.4%) BsAb-associated reports of which 132 (39.3%) were fatal. The most frequent CVAEs were shock (3.2%), bleeding (3.0%), and hypotension (2.7%). As a class, BsAbs were associated with increased reporting of hypotension (aROR: 2.15, 95% CI = 1.48-3.13) and fatal CVAEs (aROR: 2.04, 95% CI = 1.60-2.60) compared to all other drugs in the FAERS database. Individual drugs showed distinct patterns: epcoritamab showed the strongest hypotension signal (aROR: 2.37, 95% CI = 1.55-3.62) and increased fatal CVAE reporting (aROR: 2.26, 95% CI = 1.72-2.98), while mosunetuzumab was associated with atrial fibrillation/flutter (aROR: 3.04, 95% CI = 1.53-6.03), supraventricular tachycardia (aROR: 2.72, 95% CI = 1.42-5.21), and tachyarrhythmias (aROR: 2.60, 95% CI = 1.44-4.72). CVAEs occurred earlier than non-CVAEs (median, 10 vs. 16 days, P < 0.001). Cytokine release syndrome occurred in 33.4% of BsAb-related adverse events, with hypotension most commonly overlapping (53.8%), while most arrhythmias occurred independently. These findings highlight cardiovascular toxicity signals associated with BsAbs and underscore the need for continued surveillance, risk stratification, and targeted cardiovascular assessment as these expand into broader clinical practice. However, consistent with the limitations of pharmacovigilance analyses, particularly the reliance on spontaneous adverse event reporting, these observations require confirmation in prospective studies.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"19 1","pages":""},"PeriodicalIF":47.8,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13202884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148031704","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":"Standard-of-care ciltacabtagene autoleucel in earlier versus later lines of therapy for relapsed or refractory multiple myeloma: a nationwide registry analysis.","authors":"Nico Gagelmann, Hermann Einsele, Sarah Flossdorf, Samih Smaili, Klaus Metzeler, Christoph Scheid, Lars Bullinger, Sandra Sauer, Marc Raab, Justus Duyster, Hans Christian Reinhardt, Raphael Teipel, Winfried Alsdorf, Claudia Lengerke, Wolfgang Herr, Natalie Schub, Francis Ayuketang Ayuk, Florian Bassermann, Christian Schultze-Florey, Roland Schroers, Mathias Hänel, Nicola Giesen, Ahmet Elmaagacli, Andreas Burchert, Thomas Weber, Dimitrios Mougiakakos, Stefan Knop, Fabian Müller, Nicolaus Kröger, Maximilian Merz","doi":"10.1186/s13045-026-01806-6","DOIUrl":"10.1186/s13045-026-01806-6","url":null,"abstract":"<p><strong>Background: </strong>Ciltacabtagene autoleucel (cilta-cel) is a BCMA-directed chimeric antigen receptor (CAR) T-cell therapy approved for relapsed or refractory multiple myeloma (RRMM). Following the CARTITUDE-1 results in heavily pretreated patients, the randomized phase 3 CARTITUDE-4 trial demonstrated superior progression-free survival (PFS) and overall survival for cilta-cel compared with standard of care in lenalidomide-refractory patients after one to three prior lines, leading to label expansion in 2024. However, real-world data characterizing outcomes in this earlier-line indication are lacking.</p><p><strong>Methods: </strong>We analyzed all patients with RRMM receiving standard-of-care cilta-cel between 2022 and 2025 from the German Registry for Stem Cell Transplantation and Cellular Therapy. Patients were stratified by prior lines of therapy into an Early group (1-3 prior lines) and a Late group (> 3 prior lines). The primary endpoint was PFS. Secondary endpoints included overall response rate, response conversion, and safety outcomes including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome (ICANS), non-ICANS neurotoxicity, and non-relapse mortality. Prognostic associations were assessed using restricted cubic spline Cox regression and univariable Cox models.</p><p><strong>Results: </strong>Of 606 patients, 177 (30%) were treated in the Early and 429 (70%) in the Late setting. The overall response rate was 91% and 88%, with complete response in 63% and 54%, respectively. The 12-month PFS was 79% for Early and 70% for Late cilta-cel. Depth of response was the strongest predictor of PFS in both cohorts, with patients maintaining complete response showing 100% PFS at 12 months irrespective of treatment line. Extramedullary disease was adversely prognostic in both groups, whereas high-risk cytogenetics were not associated with inferior PFS in the Early group. Non-ICANS neurotoxicity occurred less frequently in the Early group (3% versus 8%), while non-relapse mortality was comparable (6% versus 7%).</p><p><strong>Conclusions: </strong>This analysis demonstrates that cilta-cel in earlier lines of therapy achieves deep responses and high PFS consistent with the CARTITUDE-4 trial. These results provide real-world evidence for the deployment of cilta-cel as early as first relapse and may be a benchmark outside prospective trials.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":" ","pages":""},"PeriodicalIF":47.8,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13307700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147982118","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":"CD20-directed antibody-drug conjugates in non-hodgkin lymphoma: translating preclinical promise into clinical reality.","authors":"Leila Omidvar, Ali Hussein Mer, Yousef Mirzaei, Mohammad-Reza Sanaye-Pasand, Saeed Jahandideh, Mahmoud Hassani, Meghdad Abdollahpour-Alitappeh","doi":"10.1186/s13045-026-01807-5","DOIUrl":"10.1186/s13045-026-01807-5","url":null,"abstract":"<p><p>Despite the paradigm-shifting success of anti-CD20 monoclonal antibodies like rituximab, limitations such as antigen loss, impaired host immune effector functions, and resistance remain key challenges in non-Hodgkin lymphoma (NHL). Antibody-drug conjugates (ADCs) targeting CD20 represent a promising strategy to overcome these limitations by delivering potent cytotoxic payloads directly to malignant B cells. However, CD20's slow internalization rate poses a unique challenge for conventional ADC design. This review provides a focused analysis of clinical- and preclinical-stage CD20-directed ADCs, examining how innovative design strategies-including cleavable linkers, membrane-permeable payloads (e.g., MMAE), site-specific conjugation, and novel platforms such as extracellular drug conjugates (EDCs) and immune-stimulating antibody conjugates (ISACs)-are being developed to circumvent the internalization barrier. We critically analyze clinical progress (MRG001 and TRS005), preclinical innovations, and future directions for translating the promise of CD20-directed ADCs into clinical reality for patients with NHL.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":" ","pages":""},"PeriodicalIF":47.8,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13307696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147930435","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":"Chinese guidelines for HER2-targeted therapy in gastric and gastroesophageal junction adenocarcinoma (2025 Edition).","authors":"Xiaotian Zhang, Yakun Wang, Muyan Cai, Fenghua Wang, Tong Xie, Jianming Ying, Weiqi Sheng, Xiangshan Fan, Xiujuan Qu, Chang Wang, Zhi Peng, Jie'er Ying, Miaozhen Qiu, Tianshu Liu, Yueping Liu, Dongmei Lin, Xiaohong Yao, Ziyu Li, Wenlong Guan, Ruihua Xu, Jin Li, Hong Bu, Lin Shen","doi":"10.1186/s13045-026-01804-8","DOIUrl":"10.1186/s13045-026-01804-8","url":null,"abstract":"<p><p>Gastric and gastroesophageal junction adenocarcinoma (GC/GEJC) poses a substantial clinical burden in China. This updated guideline introduces a refined human epidermal growth factor receptor 2 (HER2) classification system (high, intermediate, low, absent) to redefine patient stratification for targeted therapy. It integrates cutting-edge evidence on standardized detection-including immunohistochemistry, in situ hybridization, and liquid biopsy-to overcome spatial-temporal heterogeneity. Recent progress in the use of HER2-targeted agents, including monoclonal antibodies, antibody-drug conjugates, tyrosine kinase inhibitors, and bispecific antibodies, is systematically reviewed and presented to inform evidence-based clinical practice. These updates aim to optimize personalized HER2-targeted therapy and improve outcomes in GC/GEJC patients.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":" ","pages":""},"PeriodicalIF":47.8,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13308193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856560","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":"Nanotechnology-enhanced CAR-T therapy strategies in cancer, aging, and autoimmune diseases.","authors":"Hongjia Li, Jinxin Li, Xiting Liu, Xueju Wei, Xin Zeng, Qiwei Wang, Yingli Han, He Huang, Pengxu Qian","doi":"10.1186/s13045-026-01805-7","DOIUrl":"10.1186/s13045-026-01805-7","url":null,"abstract":"<p><p>Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a transformative immunotherapy, which achieves remarkable success in hematological malignancies. However, broader application of CAR-T therapy is hindered by multiple challenges, including limited efficacy in solid tumors, antigen escape, severe toxicities, and complex, costly manufacturing. Recent studies have emerged that nanotechnology offers innovative solutions to overcome barriers. In this review, we summarized how nanotechnology enhances CAR-T therapy across six dimensions: CAR design, transfection, expansion, modification, monitoring, and combination with other therapies. We discussed the applications of various nanomaterials to improve CAR-T cell function, including lipid nanoparticles, nanogels, and nanobodies. Specifically, we recapitulate that nanotechnology facilitates the generation of CAR-T cells in vivo, enables spatiotemporal control of T cells, remodels the immunosuppressive microenvironment in solid tumors, and enables dual-targeting strategies to mitigate antigen escape. Finally, we outlined the clinical application of nanotechnology in hematological malignancies and solid tumors, as well as non-malignant senescence and autoimmune diseases. Collectively, we believe the integration of nanotechnology enhances the safety and efficacy and broadens therapeutic scope, which will open a new era of precision medicine.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":" ","pages":""},"PeriodicalIF":47.8,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13307718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856236","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":"Cytokines and cancer-associated fibroblasts.","authors":"Yidu Hu, Jiaqi Liang, Lewei Duan, Junkan Zhu, Guangyao Shan, Tao Cheng, Yingting Wu, Lijie Tan, Cheng Zhan","doi":"10.1186/s13045-026-01801-x","DOIUrl":"10.1186/s13045-026-01801-x","url":null,"abstract":"<p><p>Cancer-associated fibroblast (CAF) is the dominant stromal component within the tumor microenvironment (TME), driving tumor malignancy through complex cell-to-cell communication, with cytokines serving as the fundamental communication medium. In this review, we systematically categorize cytokines into several major families-including interleukins, chemokines, growth factors, tumor necrosis factors, interferons, colony-stimulating factors, and complement system-to delineate their distinct roles in the reciprocal interactions around CAFs, tumor cells, and immune infiltrates. We explore how cytokines function as upstream signals that guide CAF activation and lineage commitment, as well as downstream effectors secreted by CAFs to promote tumor cell malignancy and reprogram the TME. Furthermore, we evaluate therapeutic strategies that target this network by reprogramming CAF functions through blockade of upstream activators or downstream mediators, and by harnessing CAFs for local cytokine delivery. Finally, we address key challenges impeding clinical translation-arising from the pleiotropy, functional redundancy, compensatory feedback loops and spatiotemporal heterogeneity that characterize cytokine signaling networks, as well as from the inherent limitations of current preclinical models-and we outline a theoretical framework for optimizing cytokine-targeted therapies in precision oncology.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":" ","pages":""},"PeriodicalIF":47.8,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13307437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816173","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":"Current and future immunotherapies for NSCLC.","authors":"Chu-Yu Zhou, Yi-Fan Qi, Hong-Ji Li, Chao Zhang, Bai-Xin Lin, Jun-Tao Lin, Yi-Long Wu, Mei-Mei Zheng, Wen-Zhao Zhong","doi":"10.1186/s13045-026-01791-w","DOIUrl":"10.1186/s13045-026-01791-w","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality worldwide. Immune checkpoint inhibitors targeting the PD-1/PD-L1 and CTLA-4 axes have fundamentally transformed its treatment landscape. This narrative review traces the evolution of NSCLC immunotherapy, from advanced-stage monotherapy and chemoimmunotherapy to its critical expansion into early-stage disease, highlighting the paradigm shift brought by neoadjuvant, adjuvant, and perioperative strategies. We examine essential clinical challenges, including optimal treatment duration, management of brain metastases, immune-related adverse events, and mechanisms of primary and acquired resistance, with a focus on genomic alterations like KRAS co-mutations with STK11 and KEAP1. Furthermore, we critically evaluate the evolving biomarker landscape, moving beyond PD-L1 to encompass circulating tumour DNA, microbiome composition, and multiparametric approaches like T-cell receptor clonality. Finally, we provide an in-depth exploration of next-generation strategies, including bispecific antibodies, novel checkpoint targets, mRNA vaccines, antibody-drug conjugates, and advanced cellular therapies. While significant progress has been made, refining biomarker-driven selection and optimizing combination sequencing remain paramount. This thorough synthesis highlights promising future directions to overcome these hurdles and improve long-term survival in NSCLC.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":" ","pages":""},"PeriodicalIF":47.8,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147773622","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":"Evolving antibody-drug conjugates in breast cancer from precision delivery to tumor microenvironment reprogramming.","authors":"Na Lu,Bin Yan,Yu-Qiang Li,Jing-Lei Wan","doi":"10.1186/s13045-026-01799-2","DOIUrl":"https://doi.org/10.1186/s13045-026-01799-2","url":null,"abstract":"Antibody-drug conjugates (ADCs) have emerged as an important therapeutic strategy for breast cancer, particularly in the context of its molecular heterogeneity. Initially developed as targeted cytotoxic delivery systems, ADCs are increasingly being explored as multifunctional platforms that may also influence the tumor microenvironment (TME). The expansion of ADC targets beyond human epidermal growth factor receptor 2 (HER2) to include molecules such as trophoblast cell surface antigen 2 (TROP-2) and human epidermal growth factor receptor 3 (HER3) has broadened the therapeutic landscape, offering new options for subtypes with limited targeted therapies, including triple-negative breast cancer (TNBC).Accumulating evidence suggests that the tumor microenvironment plays a critical role in modulating ADC efficacy and resistance. Physical barriers, immunosuppressive signaling, and stromal interactions may limit drug penetration and therapeutic response. In parallel, ADC-induced cytotoxicity has been associated with immunogenic cell death and potential remodeling of the tumor immune milieu. These insights have prompted the development of improved ADC designs, including environment-responsive linkers, optimized payloads, and rational combination strategies with immunotherapy.In this review, we summarize the evolving landscape of ADC development in breast cancer, focusing on target expansion, structural optimization, resistance mechanisms, and interactions with the tumor microenvironment. We also discuss emerging strategies aimed at enhancing therapeutic efficacy and overcoming resistance, highlighting growing interest in integrating targeted cytotoxicity with modulation of the tumor microenvironment.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"26 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147751365","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":"Five-year follow-up of patients with relapsed/refractory mantle cell lymphoma treated with anti-CD19 CAR T-cell therapy in ZUMA-2, Cohorts 1 and 2.","authors":"Javier Muñoz,Frederick L Locke,Patrick M Reagan,Andre Goy,Caron A Jacobson,Brian T Hill,John M Timmerman,Ian W Flinn,David B Miklos,John M Pagel,Marie José Kersten,Edouard Forcade,Max S Topp,Roch Houot,Amer Beitinjaneh,Dan Zheng,Mengru Chang,Wangshu Zhang,Rhine R Shen,Rita Damico Khalid,Ioana Kloos,Michael L Wang","doi":"10.1186/s13045-026-01797-4","DOIUrl":"https://doi.org/10.1186/s13045-026-01797-4","url":null,"abstract":"BACKGROUNDTreatment with brexucabtagene autoleucel (brexu-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, demonstrated a high objective response rate (93%) and complete response rate (67%) in 60 patients with relapsed/refractory mantle cell lymphoma (R/R MCL) treated in the pivotal ZUMA-2 Cohort 1 study. Subsequently, brexu-cel was approved in the United States and European Union for the treatment of adults with R/R MCL (after ≥ 2 prior therapies in the European Union). Here we report 5-year outcomes from the pivotal ZUMA-2 Cohort 1 study (N = 68), as well as two previously unpublished ZUMA-2 data sets, long-term outcomes in 10 patients who received axi-cel in Cohort 1 and in 14 patients who received a lower dose of brexu-cel in Cohort 2.METHODSThe primary endpoint for all cohorts of ZUMA-2 was objective response rate. Key secondary endpoints included duration of response (DOR), overall survival (OS), and safety. Patients could transition to a long-term follow-up study after 24 months for monitoring of survival and select adverse events possibly related to brexu-cel. Patients in Cohort 1 received a single infusion of 2 × 106 anti-CD19 CAR T cells/kg (axi-cel or brexu-cel). Patients in Cohort 2 received 0.5 × 106 anti-CD19 CAR T cells/kg (brexu-cel).RESULTSMedian follow-up for the pivotal cohort (N = 68) was 67.8 months (range, 58.2-88.6) with a median DOR of 36.5 months (n = 60), per investigator review. Median OS was 46.5 months (95% CI, 24.5-60.2; N = 68) and was 60.2 months (95% CI, 42.8-not estimable) in patients with complete response (n = 46). The 5-year incidence of cumulative relapse-related and non-relapse-related mortality was 40% (24/60) and 22% (13/60) in responders, respectively. Descriptive outcomes for axi-cel-treated patients (N = 10) and Cohort 2 (N = 14) are reported herein. No Grade 5 cytokine-release syndrome or neurologic events, subsequent T-cell malignancies, or new safety signals were reported in any patient.CONCLUSIONSPatients in ZUMA-2 continued to have durable responses after 5 years of follow-up with predictable long-term safety, supporting the continued use of brexu-cel in R/R MCL. Interpretations of outcomes in axi-cel-treated patients and Cohort 2 are not feasible due to small patient numbers and unmatched baseline characteristics.TRIAL REGISTRATIONNCT02601313 and NCT05041309.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"144 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147751363","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}