Journal of Hematology & Oncology最新文献

{"title":"Niches in cancer: from primary tumors to metastatic disease.","authors":"Zheng Chao, Xiaojing Wang, Zhihua Wang, Kongming Wu, Le Li","doi":"10.1186/s13045-026-01858-8","DOIUrl":"10.1186/s13045-026-01858-8","url":null,"abstract":"<p><p>Cancer progression does not occur in isolation: malignant-cell states and fates are shaped by specialized microenvironments, or cancer niches. Within primary tumors, vascular, stromal, immune and neural interactions create local hypoxic, metabolic and mechanical conditions that together influence malignant-cell behavior. These local environments sustain stem-like states, regulate immune surveillance and vascular remodeling, and influence dissemination and treatment response. Tumor-derived extracellular vesicles and other systemic signals connect primary tumors to distant organs, conditioning tissues before tumor-cell arrival and subsequently modulating disseminated tumor-cell seeding, dormancy, reactivation and outgrowth. Cancer niches therefore operate across spatial scales and disease stages, shaping tumor behavior in ways that cannot be explained by tumor-cell-intrinsic properties alone. Advances in single-cell and spatial profiling, organoid systems and intravital imaging are revealing their cellular composition, local architecture and evolution. In this review, we integrate primary, pre-metastatic and metastatic niche biology, examine how local environments evolve and influence one another during cancer progression, compare organ-specific metastatic niches and assess emerging therapeutic strategies. Effective niche-directed therapy will require identifying the interactions that sustain disease, showing that treatment disrupts them and determining which patients are most likely to benefit. Greater spatial, temporal and functional resolution may reveal new therapeutic vulnerabilities and create opportunities to prevent relapse and achieve more durable disease control.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"19 1","pages":""},"PeriodicalIF":47.8,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207028","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":"The advances and challenges of mRNA-LNP application in fields of hematology and oncology therapeutics.","authors":"Yuan Wang, You Ge, Yu Chen, Yongfeng Yang, Junwei Li","doi":"10.1186/s13045-026-01857-9","DOIUrl":"10.1186/s13045-026-01857-9","url":null,"abstract":"<p><p>The rapidly global deployment of COVID-19 mRNA-LNP vaccines established the clinical feasibility of combining RNA medicine with LNP delivery systems, transforming a long-standing experimental concept into a scalable therapeutic modality, previously considered impossible. Currently, the value of mRNA-LNPs has been expanding from infectious disease vaccines to cancer immunotherapy, personalized neoantigen vaccination, in vivo immune-cell engineering, protein replacement therapy, mRNA-encoded biologics and genome editing, with particular relevance to hematology and oncology. However, in hematologic and oncologic settings, therapeutic success is constrained by biological barriers that less prominent in prophylactic vaccination. Systemically administered LNPs are strongly influenced by hepatic sequestration, protein corona formation and mononuclear-phagocyte clearance; solid tumors additionally present heterogeneous vasculature, variable enhanced permeability and retention, dense extracellular matrix, elevated interstitial pressure and limited intratumoral diffusion. Hematologic applications face a different set of constraints, including access to spleen and bone marrow, selective delivery to T cells, NK cells and hematopoietic stem and progenitor cells (HSPCs), and preservation of the normal marrow niche. In this Review, we therefore discuss the molecular and principles of formulation that underpin mRNA-LNP performance in hematology and oncology, including mRNA engineering, lipid nanoparticle architecture, intracellular trafficking and selective organ targeting(SORT) delivery strategies, oncology applications spanning neoantigen vaccines, tumor-microenvironment reprogramming, mRNA-encoded biologics, gene editing and combination therapy; and hematology applications including in vivo CAR-T, CAR-NK and HSPC engineering. We further consider how inefficient extrahepatic delivery, limited endosomal escape, context-dependent reactogenicity, repeat-dosing constraints and the manufacturing complexity of individualized products continue to limit broader clinical translation. Emerging strategies, including artificial-intelligence-guided RNA and lipid design, self-amplifying RNA, circular RNA and next-generation thermostable formulations, may help address these application limitations in the fields of hematology and oncology.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"19 1","pages":""},"PeriodicalIF":47.8,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207117","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":"CAR-T-centered sequential therapy: current status, challenges, and future clinical perspectives.","authors":"Lucheng Zhou, Chengcheng Tian, Ruiqiang Du, Yizhao Chen, Zhihao Xu, Shuai Wang, Xinlei Chen, Haojie Zhang, Qianlei Wang, Qiang Cai, Jiajie Tu, Ning Lin","doi":"10.1186/s13045-026-01855-x","DOIUrl":"10.1186/s13045-026-01855-x","url":null,"abstract":"<p><p>Over recent years, chimeric antigen receptor T-cell (CAR-T) therapy has markedly improved outcomes for patients with relapsed or refractory hematological malignancies. Nevertheless, a substantial proportion of patients still experience relapse or progression after treatment, driven by factors including antigen escape, suboptimal CAR-T cell expansion and persistence, functional exhaustion, and remodeling of the tumor microenvironment. In the context of managing patients who fail initial CAR-T therapy, CAR-T-centered sequential therapy has been increasingly investigated as a potential therapeutic approach. The selection of therapeutic targets and treatment approaches may be informed by resistance mechanisms, changes in target antigen expression, and disease progression patterns following prior treatment, with the aim of prolonging disease control and improving long-term outcomes. This review summarizes recent progress in CAR-T-centered sequential therapy, with particular emphasis on same-target retreatment, switching to different antigens, multi-target stepwise CAR-T regimens, and the sequential integration of CAR-T with hematopoietic stem cell transplantation, radiotherapy, immune checkpoint inhibitors, and other immunomodulatory approaches. We further discuss the biological rationale and clinical settings of these CAR-T-centered sequential approaches in the context of antigen escape, CAR-T cell functional decline, tumor clonal evolution, and immune microenvironment remodeling. Additionally, we discuss factors that may inform the selection of subsequent regimens, including the initial treatment response, antigen status at relapse, CAR-T cell persistence, and the patient's therapeutic window, as well as the clinical settings in which these sequential approaches have been explored.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"19 1","pages":""},"PeriodicalIF":47.8,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207051","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":"AXL-directed antibody-drug conjugate therapy in soft-tissue sarcoma.","authors":"Nathan El-Ghazzi, Tony Sourisseau, Vanessa Chaire, Tom Del Ben, Marie-Alix Derieppe, Lucile Vanhersecke, Christophe Rey, Alban Bessede, Jean-Max Pasquet, Antoine Italiano","doi":"10.1186/s13045-026-01851-1","DOIUrl":"10.1186/s13045-026-01851-1","url":null,"abstract":"<p><p>AXL is a membrane-accessible receptor tyrosine kinase and a potential antibody-drug conjugate (ADC) target, but its therapeutic relevance in soft-tissue sarcoma remains incompletely defined. We evaluated the AXL-directed pyrrolobenzodiazepine ADC ADCT-601/mipasetamab uzoptirine using a sarcoma tissue microarray, patient-derived cell lines, and patient-derived xenografts. AXL expression was broad but heterogeneous, with the highest histotype-level expression in myxofibrosarcoma and undifferentiated pleomorphic sarcoma. In the patient-linked tissue-microarray cohort, AXL H-score was not associated with metastasis-free or overall survival after clinicopathologic adjustment. ADCT-601 was substantially more potent than a non-targeting anti-gp120 control ADC carrying the same SG3199-containing payload. Free-payload sensitivity varied between cell lines, indicating that intrinsic payload susceptibility contributes to activity, while the payload-matched comparison supports an additional effect of AXL-mediated delivery. ADCT-601 induced cell-cycle perturbation, apoptosis, and γ-H2AX accumulation. Combination experiments identified enhanced activity with DNA damage-response inhibition, particularly ATR inhibition, and in vivo studies supported antitumor activity in two sarcoma xenograft models. These data support biomarker-enriched development of next-generation AXL-directed ADC strategies while emphasizing antigen heterogeneity and therapeutic-index optimization.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"19 1","pages":""},"PeriodicalIF":47.8,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207033","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":"Novel antibody-based regimens for large B-cell lymphoma: latest updates from the 2026 ASCO Annual Meeting.","authors":"Gengcong Luo, Hongbin Jiang, Zegeng Chen, Chunjia Zhang","doi":"10.1186/s13045-026-01854-y","DOIUrl":"10.1186/s13045-026-01854-y","url":null,"abstract":"<p><p>Large B-cell lymphoma (LBCL) encompasses a biologically and clinically heterogeneous group of aggressive B-cell lymphomas, and outcomes remain poor in high-risk and relapsed/refractory settings. Beyond conventional anti-CD20 monoclonal antibodies, the Fc-modified anti-CD19 antibody tafasitamab, the CD79b-directed antibody-drug conjugate polatuzumab vedotin, and CD20×CD3 bispecific antibodies are expanding treatment options across disease stages and patient populations. At the 2026 ASCO Annual Meeting, the phase 3 frontMIND trial provided randomized evidence for tafasitamab plus lenalidomide and R-CHOP in newly diagnosed high-risk disease, while OLYMPIA-3 further explored CD20×CD3 bispecific antibody intensification in the same setting. In older or treatment-unfit patients, early-phase nonrandomized studies of epcoritamab plus R-mini-CVP and mosunetuzumab monotherapy suggested the feasibility of chemotherapy-attenuated and chemotherapy-free approaches. In relapsed/refractory LBCL, SUNMO established a progression-free survival advantage for mosunetuzumab plus polatuzumab vedotin in autologous stem-cell transplantation (ASCT)-ineligible disease, whereas EPCORE NHL-2 supported epcoritamab-based salvage therapy in transplant-eligible patients. Collectively, these findings broaden the role of antibody-based regimens from frontline intensification and reduced-intensity treatment to nontransplant and transplant-directed salvage. Longer follow-up and randomized comparisons are needed to establish response durability, refine patient selection, and define optimal treatment sequencing.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"19 1","pages":""},"PeriodicalIF":47.8,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149194776","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 therapies for acute myeloblastic leukemia","authors":"Jennifer Marvin-Peek,Farhad Ravandi","doi":"10.1186/s13045-026-01849-9","DOIUrl":"https://doi.org/10.1186/s13045-026-01849-9","url":null,"abstract":"","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"16 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088430","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":"T-cell-redirecting therapies in early relapsed multiple myeloma: a systematic review and network meta-analysis","authors":"Maximilian Merz,Joao Tadeu Souto Filho,Peter M. Voorhees,Hermann Einsele,Fredrik Schjesvold,Edward R. Scheffer Cliff,Maria-Victoria Mateos,Vania Hungria,Yael C. Cohen,Carlos Fernández de Larrea,Meral Beksac,Ola Landgren,Saad Z. Usmani,Luciano J. Costa,Nico Gagelmann","doi":"10.1186/s13045-026-01850-2","DOIUrl":"https://doi.org/10.1186/s13045-026-01850-2","url":null,"abstract":"Abstract Background Chimeric antigen receptor T cells and bispecific antibodies, are moving from late-line salvage into early relapsed multiple myeloma. Indirect comparisons in heavily pretreated patients have favored cell therapy, but whether that hierarchy holds in early relapse is unknown. Methods We analyzed randomized phase 3 trials comparing a T-cell-redirecting therapy against a daratumumab-pomalidomide-dexamethasone-type control after at least one prior line. Pseudo-individual patient time-to-event data were reconstructed from published survival curves. Regimens were compared indirectly in Bayesian network meta-analyses reported under fixed-effect and random-effects assumptions, re-estimated in a frequentist graph-theoretical model. Control-arm dispersion was quantified by random-effects synthesis of median progression-free survival. Overall survival was additionally analyzed as restricted mean survival differences at 24 and 36 months. Safety and a cost-consequence analysis were assessed descriptively (PROSPERO: CRD420261431847). Results Four trials (2,174 patients) investigating ciltacabtagene autoleucel, teclistamab-daratumumab, and talquetamab-daratumumab with or without pomalidomide were included. Control-arm median progression-free survival spanned 9.9 to 24.4 months (I-squared 91%). Under fixed effects, teclistamab-daratumumab ranked first for progression-free survival (P-score 98%, the mean probability of outranking a competing treatment rather than the probability of being best) and separated from talquetamab-daratumumab (hazard ratio 0.55, 95% credible interval 0.34 to 0.88). Once between-trial heterogeneity was admitted, every contrast crossed unity (versus ciltacabtagene autoleucel 0.62, 0.21 to 1.81). Overall survival was concordant under both models (teclistamab-daratumumab versus ciltacabtagene autoleucel 0.94, 0.55 to 1.62), with restricted mean survival gains over control of 0.7 to 1.6 months at 24 months and rankings between 56% and 70%. Toxicity profiles differed across modalities, although their overall burden cannot be reliably compared across trials. Cost per progression-free month, computed against a population-standardized denominator, was lowest for cilta-cel and converged with the bispecific regimens only under short, fixed treatment durations. Conclusions Randomized evidence in early relapse does not establish an efficacy hierarchy among these regimens. Progression-free survival estimates favored teclistamab-daratumumab, but no contrast was robust to plausible between-trial heterogeneity, and equivalence could not be demonstrated. Until comparative data exist, treatment selection cannot rest on efficacy data alone and will be informed by patient- and disease-related factors, toxicity, sequencing, access, and cost.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"1 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088429","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":"Updates in CAR-T and TCR-T therapy for solid tumors from the 2026 ASCO Annual Meeting","authors":"Oriol Mirallas,Ecaterina E. Dumbrava","doi":"10.1186/s13045-026-01852-0","DOIUrl":"https://doi.org/10.1186/s13045-026-01852-0","url":null,"abstract":"","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"14 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088431","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":"Outcomes of front-line tagraxofusp in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) in a real-world scenario","authors":"Jan C. Schroeder,Philipp Faustmann,Snjezana Janjetovic,Anna Ossami Saidy,Hanna K. Zieger,Giuliano Filippini Velazquez,Thomas Melchardt,David Baden,Hristo Boyadzhiev,Tim Sauer,Christoph Schliemann,Jan-Henrik Mikesch,Niklas Gebauer,Susanne von Kroge,Paul J. Bröckelmann,Friederike Hildebrand,Veit Bücklein,Rebecca Wurm-Kuczera,Ulrich Keller,Thomas Pabst,Maher Hanoun,Claudia Lengerke,Evgenii Shumilov,Georg Lenz,Ulrike Bacher,Philipp Berning","doi":"10.1186/s13045-026-01848-w","DOIUrl":"https://doi.org/10.1186/s13045-026-01848-w","url":null,"abstract":"Abstract Tagraxofusp (TAG), a CD123-directed protein-drug conjugate, is approved in front-line and relapsed/refractory blastic plasmacytoid dendritic cell neoplasm (BPDCN). Multicenter real-world outcomes and the contribution of up-front consolidation post-TAG remain less defined. We retrospectively analyzed 32 patients with BPDCN treated with frontline TAG (2019–2024) across 13 tertiary centers, contextualized against a historical cohort treated before TAG availability ( n  = 40). Patients were elderly (median age 71.5 years) with advanced disease, including skin (93.8%), bone marrow (84.4%), and peripheral blood involvement (53.1%). The overall response rate to TAG was 82.1%, with complete responses in 60.7%. Capillary leak syndrome occurred in 53.1% (grade ≥ 3 in 47.1%), with no unexpected safety signals. With a median follow-up of 18.4 months, 2-year overall survival (OS) and progression-free survival were 40.5% and 30.4%. Nearly half of patients proceeded to allogeneic stem cell transplantation post-TAG, associated with improved survival consistent with the primary analysis and landmark-adjusted analyses (HR 0.25 [0.06–1.14]; p  = 0.073). Propensity score–matched comparison with the Non-TAG cohort showed comparable 2-year OS (59.4% vs 60.8%; p  = 0.9). Frontline TAG was not associated with OS in pooled multivariable regression (HR 0.89 [0.37–2.15]; p  = 0.803), while peripheral blood involvement remained associated with reduced OS (HR 2.63, 95% CI 1.1–6.27; p  = 0.03). In this large multicenter real-world cohort, frontline TAG achieved high response rates with manageable toxicity. While unmeasured selection may contribute to the higher transplantation rate after TAG, durable remissions were achieved in patients undergoing post-TAG consolidation, supporting TAG as an induction and bridging strategy to allogeneic stem cell transplantation.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"36 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088432","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":"Mitochondrial genetic variation as a novel predictor of graft-versus-host disease after stem-cell transplantation in myelodysplastic neoplasms","authors":"Shahram Arsang-Jang,Tao Zhang,Maryam Rafati,Yung-Tsi Bolon,Stephen R. Spellman,Zhongyuan Chen,Kristine Jones,Jia Liu,Najla El Jurdi,Xiaowu Gai,Raul Urrutia,Shahinaz M. Gadalla,Paul L. Auer,Wael Saber,Jing Dong","doi":"10.1186/s13045-026-01846-y","DOIUrl":"https://doi.org/10.1186/s13045-026-01846-y","url":null,"abstract":"","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"8 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088549","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}