BMC Cancer最新文献

{"title":"Co-expression of non-signaling CARs enhances EGFRvIII-specific CAR T-cell cytotoxicity against head and neck squamous cell carcinoma.","authors":"Kathleen Grueter, Nicole Sander, Luisa Coen, Saskia Hüsken, Eileen Kleinfelder, Corinna Haist, Franziska Blaeschke, Kathrin Scheckenbach, Cornelia Monzel, Helmut Hanenberg, Constanze Wiek","doi":"10.1186/s12885-026-17058-z","DOIUrl":"10.1186/s12885-026-17058-z","url":null,"abstract":"<p><strong>Background: </strong>Head and neck squamous cell carcinoma (HNSCC) remains difficult to treat due to heterogeneous antigen expression and an immunosuppressive tumor microenvironment. The epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific splice form with no detectable protein expression in normal tissues. Nevertheless, its low and often heterogeneous expression in HNSCC has limited its utility as target antigen for immunological therapies using chimeric antigen receptor (CAR) T-cells. In contrast, full-length EGFR is frequently overexpressed in HNSCC, but its expression in normal tissues prevents its use as a directly activating CAR target. Thus, we investigated here whether EGFR can instead provide additional target antigen engagement as a non-signaling CAR (nsCAR) for EGFRvIII CARs. The nsCAR was derived from Cetuximab, an EGFR-binding monoclonal antibody whose epitope is retained in EGFRvIII and was co-expressed with different EGFRvIII-specific signaling CAR to investigate whether additional receptor engagement could enhance target-cell recognition and cytotoxicity.</p><p><strong>Methods: </strong>Primary human T-cells were engineered to express EGFRvIII-specific CARs alone or in combination with EGFR-directed nsCARs. Functional activity was evaluated using in vitro cytotoxicity assays, time-resolved killing dynamics, and fluorescence microscopy to assess immunological synapse (IS) formation in HNSCC cell lines with defined levels of EGFRvIII expression.</p><p><strong>Results: </strong>EGFRvIII CAR T-cells exhibited clear target antigen density-dependent cytotoxicity. Co-expression of the EGFR nsCAR specifically enhanced tumor cell killing in selected CAR and target antigen combinations, with the strongest effects observed under conditions of limited baseline CAR activity, whereas the nsCAR alone was non-cytotoxic. Fluorescence imaging revealed co-localization of CAR and nsCAR molecules at the T-cell-target-cell contact interface.</p><p><strong>Conclusions: </strong>EGFR nsCAR co-expression can provide a modular strategy to enhance EGFRvIII CAR T-cell cytotoxicity under conditions of limited target antigen availability. These findings provide an in vitro proof of concept for additional target engagement through a non-signaling receptor and warrant further evaluation in more complex preclinical models.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"26 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13625461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into the survival impact of delayed immunochemotherapy in newly diagnosed diffuse large B-cell lymphoma: results from a nationwide registry study.","authors":"Susanne von Kroge, Nils Janis Steinhaus, Carsten Bokemeyer, Fabian Tetzlaff, Hanna Walk, Henrik Kusche, Frederik Peters","doi":"10.1186/s12885-026-17024-9","DOIUrl":"10.1186/s12885-026-17024-9","url":null,"abstract":"<p><strong>Background: </strong>The prognostic impact of the diagnosis-to-treatment interval (DTI) in diffuse large B-cell lymphoma (DLBCL) remains controversial. We investigated the association between DTI and three-year all-cause mortality in a nationwide cohort.</p><p><strong>Methods: </strong>We conducted a retrospective population-based cohort study using harmonised German cancer registry data (2020-2023), with vital status follow-up until December 2024. Patients with a first primary DLBCL diagnosis were included. Kaplan-Meier analyses and Cox regression assessed DTI in relation to survival, unadjusted and adjusted for patient, tumor, and structural characteristics. Missing International Prognostic Index (IPI) data formed a separate category, with complete-case and imputation sensitivity analyses.</p><p><strong>Results: </strong>Of 16,443 patients, 10,872 initiated systemic therapy within 56 days (eight weeks) and entered the primary analysis. Median age was 71 years, 44.2% were female, and median follow-up was 1.5 years. Three-year overall survival ranged from ~ 63% to 75% across the five treatment-week groups. Compared with week 1, later initiation was associated with progressively lower hazard of death (week 3: HR 0.72, 95% CI 0.64-0.81; week 4: HR 0.63, 0.55-0.72; weeks 5-8: HR 0.62, 0.54-0.70). Lower-risk IPI predicted better survival (low risk: HR 0.24, 0.17-0.34 vs high risk). Later initiation was predicted by low-risk IPI (+ 7.89 days), older age (+ 0.62 days/SD), and surviving the first year (+ 3.26 days).</p><p><strong>Conclusion: </strong>Early treatment in DLBCL is primarily driven by adverse disease characteristics. A residual association between longer DTI and improved survival persisted after IPI adjustment, suggesting DTI may be an independent prognostic factor in less aggressive disease.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"26 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Survival of myelodysplastic syndrome patients after azacitidine therapy.","authors":"Kanticha Thammagul, Suppalux Limpiwattakee, Pichika Chantrathammachart, Teeraya Puavilai, Suporn Chuncharunee, Pimjai Niparuck","doi":"10.1186/s12885-026-16993-1","DOIUrl":"10.1186/s12885-026-16993-1","url":null,"abstract":"","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"26 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative effectiveness of neoadjuvant therapy combined with stent placement versus stent alone in obstructive colorectal cancer: a multicenter retrospective analysis.","authors":"Zhuo Han, Bo Zhang, Shiqi Liu, Tao Wu, Qing Qiao, Xianli He, Jiagang Han, Nan Wang","doi":"10.1186/s12885-026-16728-2","DOIUrl":"10.1186/s12885-026-16728-2","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study was to evaluate the impact of self-expandable metal stents (SEMS) and neoadjuvant therapy (NAT) for obstructive colorectal cancer (CRC).</p><p><strong>Methods: </strong>This multicenter, retrospective study analyzed 154 patients with obstructive CRC from three centers between 2011 and 2025. Patients were allocated to either a NAT combined with SEMS group (n = 93) or a SEMS-alone group (n = 61). Short-term procedural outcomes, pathological tumor response, long-term survival, and the impact of the time interval from stenting to surgery were evaluated between groups and across two time periods (2011-2020 vs. 2021-2025).</p><p><strong>Results: </strong>Baseline characteristics were largely comparable between groups. The NAT group demonstrated significantly lower intraoperative stoma rates (8.6% vs. 29.0%, P = 0.031) and postoperative complication rates (8.6% vs. 29.0%, P = 0.031) in the 2011-2020, advantages that persisted in the 2021-2025. Pathological assessment revealed a superior tumor response in the 2021-2025, with 20.7% achieving TRG 0-1 and significantly higher rates of T and N downstaging (39.7% and 60.3%) compared to the 2011-2020. Although survival benefits were not significant in the 2011-2020 period, NAT may be associated with a significant improvement in overall survival (OS) in the 2021-2025 cohort (P = 0.013). Analysis of surgical timing identified an optimal interval of 14-21 days related to OS for the SEMS group, whereas for NAT patients, an interval exceeding 90 days was associated with worse disease-free survival (DFS).</p><p><strong>Conclusion: </strong>SEMS-NAT for obstructive CRC may is an important factor for improved surgical quality and OS benefit in 2021-2025. This study provides crucial evidence for optimizing treatment strategy by recommending a surgery interval.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"26 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Family-centred psycho-oncological counselling for parents with cancer: a longitudinal secondary data analysis of psychological distress, family functioning and parental concerns.","authors":"Wiebke Geertz, Laura Inhestern, Isabelle Scholl, Corinna Bergelt","doi":"10.1186/s12885-026-17004-z","DOIUrl":"10.1186/s12885-026-17004-z","url":null,"abstract":"<p><strong>Background: </strong>When a parent is diagnosed with cancer, it can place a significant burden on the entire family. The aim of this study is therefore to analyse the psychological distress experienced over time among cancer patients or their partners who are raising minor children and who utilize a family-oriented counselling service (COSIP), and to compare these data with those of a group receiving routine psycho-oncological care (PO).</p><p><strong>Methods: </strong>We conducted a secondary, longitudinal observational study based on routine care data from users of an outpatient psycho-oncological clinic. The database comprised assessments at baseline and at 6- and 12-month follow-ups, including measures of distress, anxiety and depression for COSIP and PO users. For COSIP users additional data on health-related quality of life (HRQoL), parental concerns, and family functioning was included. We conducted descriptive analyses and examined baseline group differences using t-tests and Pearson's chi-square tests. Longitudinal trajectories were analysed using linear mixed-effects models.</p><p><strong>Results: </strong>Data from n = 34 parents who had registered themselves and their families for a COSIP counselling session between 2020 and 2022 were included in the analyses. Among the COSIP users, the time since the initial diagnosis was shorter on average (p = .017) and the parents were separated less frequently (p = .015) than in the group of PO users (n = 34). At baseline, PO and COSIP users exhibited elevated levels of psychological burden, with over 80% of parents reporting clinically significant distress, 54% presenting with moderate to severe anxiety symptoms, and 50% showing elevated levels of depressive symptoms. In the adjusted model, a significant main effect of time, for distress F(2, 107.24) = 14.72, p < .001, depression F(2, 69.61) = 12.27, p < .001 and anxiety F(2, 84.11) = 17.02, p < .001, but no group difference were found. We identified a significant effect of time for parental concerns F(2, 17.24) = 7.41, p = .006, parental HRQoL F(2, 31.52) = 4.34, p = .022 and children's HRQoL F(2, 28.11) = 5.21, p = .012 among COSIP users.</p><p><strong>Conclusion: </strong>Parents who are confronted with a cancer diagnosis show high levels of psychological distress. Over time, a significant decrease in psychological distress among both groups and family-related outcomes in COSIP users was identified. Interestingly, no significant differences were observed between the groups, suggesting that the type of psycho-oncological support (individual or family-centred) may not differentially affect parental burden.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"26 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of adding ovarian function suppression to adjuvant endocrine therapy in premenopausal patients with hormone receptor-positive, HER2-positive breast cancer who have undergone neoadjuvant therapy: a single-center experience.","authors":"Okan Aydin, Hale Gulcin Yildirim Dogan, Sermin Dinc Sonusen, Mert Erciyestepe, Ahmet Emin Ozturk, Asli Buyukkuscu, Zehra Sucuoglu Isleyen, Kayhan Erturk","doi":"10.1186/s12885-026-17017-8","DOIUrl":"10.1186/s12885-026-17017-8","url":null,"abstract":"<p><strong>Purpose: </strong>The role of ovarian function suppression (OFS) in premenopausal patients with hormone receptor (HR)-positive, HER2-positive breast cancer remains unclear in the era of anti-HER2 therapy. This study evaluated the effect of adding OFS to adjuvant endocrine therapy on outcomes in premenopausal patients receiving neoadjuvant anti-HER2 therapy.</p><p><strong>Methods: </strong>We retrospectively reviewed 138 premenopausal patients with HR-positive/HER2-positive non-metastatic breast cancer treated with anti-HER2-based neoadjuvant therapy and surgery between 2015 and 2024. Patients were grouped by receipt of OFS during the adjuvant period. The primary endpoints were disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS); pathological complete response (pCR; ypT0/is ypN0) was evaluated as a secondary endpoint.</p><p><strong>Results: </strong>Among 138 patients, 60 (43.5%) received OFS. Overall, 42% achieved pCR. After a median follow-up of 56 months, 20 patients (14.5%) recurred or developed metastasis, and 11 (8%) died. Five-year OS rates were 93.9% with OFS and 85.8% without (p = 0.4); DFS rates were 80.7% and 81.3% (p = 0.9). Patients with pCR had excellent survival (5-year OS 100%) irrespective of OFS. In those with residual disease, OFS was associated with numerically higher OS (89.9% vs. 77.6%) but no DFS benefit. Multivariate analysis showed no independent association between OFS and survival outcomes.</p><p><strong>Conclusion: </strong>In this retrospective real-world study, no independent association between OFS and survival outcomes was observed in premenopausal patients with HR-positive/HER2-positive breast cancer treated with anti-HER2-based neoadjuvant therapy. Patients achieving pCR had excellent prognoses regardless of OFS use. Given the limited statistical power and the predominantly tamoxifen-treated cohort, these findings should be interpreted with caution. Prospective studies are warranted to better define the role of OFS in this patient population.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"26 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics profiling reveals sphingolipid metabolism reprogramming of tumor-conditioned MDSCs in cervical cancer.","authors":"Qiuwen Mai, Chudan Chi, Xiaojun Wang, Yili Chen, Qiaojian Zou, Qianrun Chen, Feitianzhi Zeng, Mengxun Wei, Yanfei Chen, Aiting Wang, Yan Liao, Yuzhou Xiao, Xinjie Li, Qing Yan, Liping Zhan, Hongsuo Wei, Xu Jing, Qiqiao Du, Junxiu Liu","doi":"10.1186/s12885-026-16914-2","DOIUrl":"10.1186/s12885-026-16914-2","url":null,"abstract":"<p><strong>Background: </strong>Myeloid-derived suppressor cells (MDSCs) play a crucial role in the tumor microenvironment (TME) of cervical cancer (CC), yet the mechanisms underlying their reprogramming remain poorly understood.</p><p><strong>Methods: </strong>To explore the immune microenvironment change in CC, we applied TCGA-CC immune microenvironment infiltration estimation analysis via Timer 2.0 online datasets. To generate tumor-conditioned MDSCs, the culture medium of MDSCs was supplemented with supernatants from the murine CC cell lines U14 and TC1, respectively. CCK8 assays, transwell migration experiments and qPCR were executed to test the proliferation, migration and iNOS expression. We then conducted proteomics and metabolomics analyses of tumor-conditioned MDSCs.</p><p><strong>Results: </strong>The tumor immune microenvironment analysis identified MDSCs as key components, predicting poor prognosis in CC. Tumor-conditioned MDSCs presented higher proliferation, migration and iNOS expression. Proteomics and metabolomics analyses showed significant changes in lipid metabolism, especially sphingolipid metabolism. Specifically, the Kng1-sphingosine 1-phosphate axis was identified as a central protein-metabolite regulatory node. Gain- and loss-of-function experiments confirmed that KNG1 modulates multiple cellular processes including proliferation, migration, iNOS expression, and sphingosine 1-phosphate production.</p><p><strong>Conclusion: </strong>Our findings uncover sphingolipid metabolic reprogramming as a key mechanism in MDSCs-mediated immune suppression, and propose the Kng1-sphingosine 1-phosphate network as a potential therapeutic target for CC treatment.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"26 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: HLA Class II molecule HLA-DRA identifies immuno-hot tumors and predicts the therapeutic response to anti-PD-1 immunotherapy in NSCLC.","authors":"Jie Mei, Guanyu Jiang, Yundi Chen, Yongrui Xu, Yuan Wan, Ruo Chen, Feng Liu, Wenjun Mao, Mingfeng Zheng, Junying Xu","doi":"10.1186/s12885-026-16779-5","DOIUrl":"10.1186/s12885-026-16779-5","url":null,"abstract":"","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"26 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13584547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profiling proteomic responses in small intestinal neuroendocrine tumor GOT1 after [¹⁷⁷Lu]Lu-DOTATATE therapy.","authors":"Johan K E Spetz, Mikael E Montelius, Evelin Berger, Julia A M Johansson, Nishte Rassol, Maria Ljungberg, Eva B Forssell-Aronsson","doi":"10.1186/s12885-026-16975-3","DOIUrl":"10.1186/s12885-026-16975-3","url":null,"abstract":"<p><strong>Background: </strong>Peptide receptor radionuclide therapy with [¹⁷⁷Lu]Lu-DOTATATE is an established treatment for somatostatin receptor-expressing neuroendocrine tumors. Although strong anti-tumor effects have been demonstrated in experimental models, curative responses in patients remain limited. Improved understanding of the molecular responses induced by [¹⁷⁷Lu]Lu-DOTATATE may help identify strategies for treatment optimization. This study aimed to characterize proteomic alterations in GOT1 small intestinal neuroendocrine tumor xenografts following [¹⁷⁷Lu]Lu-DOTATATE therapy.</p><p><strong>Methods: </strong>GOT1 tumor-bearing BALB/c nude mice received a non-curative intravenous administration of 15 MBq [¹⁷⁷Lu]Lu-DOTATATE or saline control. Tumors were collected 1 or 13 days after treatment to represent early response and regrowth phases. Tumor volumes were monitored using magnetic resonance imaging. Proteomic profiling was performed using liquid chromatography tandem mass spectrometry with tandem mass tag labeling. Differential protein expression was analyzed using Welch's t-test with significance defined as fold change ≥ 1.5 and p < 0.01. Functional enrichment and pathway analyses were conducted using Gene Ontology annotation and Ingenuity Pathway Analysis.</p><p><strong>Results: </strong>Treatment induced a transient reduction in tumor volume followed by regrowth. In total, 3861 proteins were quantified, of which 155 showed significantly altered expression after treatment. Affected proteins were associated with cytoskeletal organization, oxidative stress response, protein metabolism, and systemic regulation. Pathway analyses identified inhibition of several signaling pathways linked to cell migration and invasiveness, including RhoA, Rac, integrin, and CXCR4 signaling. Upstream regulator analysis suggested activation of RABL6 and inhibition of p53 signaling during tumor regrowth. Proteins related to endoplasmic reticulum stress and ubiquitin-proteasome activity were also altered. Selected findings were validated by ELISA.</p><p><strong>Conclusions: </strong>[¹⁷⁷Lu]Lu-DOTATATE therapy induced extensive proteomic changes in GOT1 tumors, including suppression of pathways associated with invasiveness and modulation of p53- and stress-related signaling. These findings suggest potential therapeutic benefits of combining [¹⁷⁷Lu]Lu-DOTATATE with agents targeting p53 regulation or endoplasmic reticulum stress pathways to improve treatment efficacy in neuroendocrine tumors.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"26 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13584284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148987950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Belantamab mafodotin plus venetoclax in t(11;14)-positive relapsed or refractory multiple myeloma - the BELI(E)VE trial.","authors":"Christoph Schaefers, Cyrus Khandanpour, Mathias Hänel, Miriam Kull, Winfried Alsdorf, Abdulaziz Kamili, Ricardo Kosch, William Krüger, Stephan Bohl, Elias Karl Mai, Christof Scheid, Hermann Einsele, Monika Brüggemann, Anna Suling, Antonia Zapf, Carsten Bokemeyer, Katja Weisel, Lisa Leypoldt","doi":"10.1186/s12885-026-16905-3","DOIUrl":"10.1186/s12885-026-16905-3","url":null,"abstract":"<p><strong>Background: </strong>Multiple myeloma (MM) is a widely incurable B-cell malignancy that predominantly affects older adults, representing 10% of hematologic cancers. Despite advancements in therapy that have significantly extended median overall survival (OS), MM remains a clinical challenge with poor prognosis for patients refractory to multiple drug classes. There is a critical need for innovative and personalized treatments, including for patients with translocation (11;14), a subgroup characterized by specific therapeutic vulnerabilities. Combined targeting of B-cell maturation antigen (BCMA) and BCL-2 presents a promising personalized treatment strategy for inducing deep remissions and improving outcomes in this specific subgroup.</p><p><strong>Methods: </strong>The BELI(E)VE trial (NCT05853965) is a German investigator-initiated, prospective, multicenter, open-label phase I/IIa study designed to evaluate the combination of belantamab mafodotin and venetoclax, with or without dexamethasone, in patients with relapsed or refractory multiple myeloma (RRMM) with ≥1 prior treatment line and t(11;14) translocation. The study consists of a dose escalation phase (phase I) to determine the recommended phase 2 dose (RP2D), followed by a dose expansion phase (phase IIa) to assess clinical activity at the RP2D. The phase I portion employs a traditional 3+3 design across four dose levels, while the phase IIa expansion will include 25 additional patients treated at the RP2D. Safety, tolerability, and preliminary efficacy will be evaluated through comprehensive assessments, including assessment for minimal residual disease negativity and ocular exams.</p><p><strong>Discussion: </strong>The BELI(E)VE trial aims to establish a novel personalized therapeutic approach for a specific subset of MM patients by combining belantamab mafodotin and venetoclax. This combination targets BCMA and BCL-2, potentially inducing deep and durable remissions. The study will provide critical data on the safety and efficacy of this combination, aiming to improve outcomes in t(11;14)-positive RRMM patients. The translational component, examining circulating tumor cells and mitochondrial activity, may identify mechanisms of resistance and response, guiding future personalized therapeutic strategies.</p><p><strong>Trial registration: </strong>NCT05853965 (2023-04-22).</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"26 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}