Journal of Hematology & Oncology最新文献

{"title":"Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition","authors":"Antonino Glaviano, Hannah Si-Hui Lau, Lukas M. Carter, E. Hui Clarissa Lee, Hiu Yan Lam, Elena Okina, Donavan Jia Jie Tan, Wency Tan, Hui Li Ang, Daniela Carbone, Michelle Yi-Hui Yee, Muthu K. Shanmugam, Xiao Zi Huang, Gautam Sethi, Tuan Zea Tan, Lina H. K. Lim, Ruby Yun-Ju Huang, Hendrik Ungefroren, Elisa Giovannetti, Dean G. Tang, Tullia C. Bruno, Peng Luo, Mads Hald Andersen, Bin-Zhi Qian, Jun Ishihara, Derek C. Radisky, Salem Elias, Saurabh Yadav, Minah Kim, Caroline Robert, Patrizia Diana, Kurt A. Schalper, Tao Shi, Taha Merghoub, Simone Krebs, Anjali P. Kusumbe, Matthew S. Davids, Jennifer R. Brown, Alan Prem Kumar","doi":"10.1186/s13045-024-01634-6","DOIUrl":"https://doi.org/10.1186/s13045-024-01634-6","url":null,"abstract":"The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, and signaling molecules that interact to promote tumor growth and therapeutic resistance. Elucidating the intricate interactions between cancer cells and the TME is crucial in understanding cancer progression and therapeutic challenges. A critical process induced by TME signaling is the epithelial-mesenchymal transition (EMT), wherein epithelial cells acquire mesenchymal traits, which enhance their motility and invasiveness and promote metastasis and cancer progression. By targeting various components of the TME, novel investigational strategies aim to disrupt the TME’s contribution to the EMT, thereby improving treatment efficacy, addressing therapeutic resistance, and offering a nuanced approach to cancer therapy. This review scrutinizes the key players in the TME and the TME's contribution to the EMT, emphasizing avenues to therapeutically disrupt the interactions between the various TME components. Moreover, the article discusses the TME’s implications for resistance mechanisms and highlights the current therapeutic strategies toward TME modulation along with potential caveats.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"42 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974786","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":"Global status and attributable risk factors of breast, cervical, ovarian, and uterine cancers from 1990 to 2021","authors":"Tianye Li, Haoxiang Zhang, Mengyi Lian, Qionghua He, Mingwei Lv, Lingyun Zhai, Jianwei Zhou, Kongming Wu, Ming Yi","doi":"10.1186/s13045-025-01660-y","DOIUrl":"https://doi.org/10.1186/s13045-025-01660-y","url":null,"abstract":"Female-specific cancers, particularly breast, cervical, ovarian, and uterine cancers, account for nearly 40% of all cancers in women. This study aimed to analyze the global epidemiological trends of these cancers from 1990 to 2021, offering insights into their evolving patterns and providing valuable information for health policymakers to allocate healthcare resources more effectively. Data from the Global Burden of Disease Study 2021 (GBD 2021) were used to comprehensively assess the global incidence, mortality, and disability-adjusted life years (DALYs) of female-specific cancers. Age-standardized rates facilitated cross-regional comparisons, accounting for differences in population size and demographics. The socio-demographic index (SDI) was employed to categorize regions and evaluate correlations between cancer burden and economic level. In addition, risk factors attributable to female-specific cancer deaths and DALYs were assessed based on the comparative risk assessment model of the GBD project. From 1990 to 2021, the global burden of female-specific cancers increased at varying rates. In 2021, breast cancer accounted for 2.08 million incident cases, 0.66 million deaths, and 20.25 million DALYs globally. In comparison, cervical, ovarian, and uterine cancers had lower burdens, with 0.67 million, 0.30 million, and 0.47 million incident cases, respectively. Age-standardized rates of breast, ovarian, and uterine cancers showed positive correlations with SDI, while cervical cancer exhibited a negative correlation. Attributable risk factors for breast cancer-associated deaths in 2021 included dietary risks, high body-mass index (BMI), high fasting plasma glucose, alcohol use, tobacco use, and low physical activity. Additional risk factors were unsafe sex and tobacco use for cervical cancer, high BMI and occupational risks for ovarian cancer, and high BMI for uterine cancer. The burden of female-specific cancers has increased in recent decades, with significant demographic and regional discrepancies. These findings highlight the urgent need for targeted public health interventions to mitigate the global impact of these cancers.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"3 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142940023","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 phase II trial of anlotinib plus EGFR-TKIs in advanced non-small cell lung cancer with gradual, oligo, or potential progression after EGFR-TKIs treatment (CTONG-1803/ALTER-L001)","authors":"Hua-Jun Chen, Hai-Yan Tu, Yanping Hu, Yun Fan, Guowu Wu, Shundong Cang, Yi Yang, Nong Yang, Rui Ma, Gaowa Jin, Ximing Xu, Anwen Liu, Shubin Tang, Ying Cheng, Yan Yu, Chong-Rui Xu, Qing Zhou, Yi-Long Wu","doi":"10.1186/s13045-024-01656-0","DOIUrl":"https://doi.org/10.1186/s13045-024-01656-0","url":null,"abstract":"The study is to evaluate the efficacy and safety of combined anlotinib and EGFR-tyrosine kinase inhibitors (TKIs) in patients with advanced non-small cell lung cancer (NSCLC) who had gradual, oligo, or potential progression after previous EGFR-TKIs treatment. We conducted an open-label, single-arm, multicenter, phase II trial in China. Eligible patients were 18–75 years old with histologically or cytologically confirmed NSCLC who were EGFR mutation positive and showed gradual, oligo, or potential progression after EGFR-TKIs. Anlotinib (12 mg/day) was administered orally for 2 weeks and then off 1 week in a 3-week cycle. EGFR-TKIs were continue used. The primary endpoint was progression-free survival (PFS). The secondary endpoints included 6- and 12-month PFS rate, objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. From July 2019 to December 2022, 120 patients were enrolled. The median PFS (mPFS) was 9.1 months (95% CI 6.8–11.7). The PFS rates at 6 and 12 months was 68.5% and 38.8% respectively. For 86 patients with first-line 1st /2nd generation EGFR-TKIs, the mPFS was 9.2 months (95% CI 6.7–12.6). For 32 patients with first-line 3rd generation EGFR-TKIs, the mPFS was 10.3 months (95% CI 6.1–13.3). Overall ORR and DCR were 6.7% (95% CI 2.9–12.7) and 87.5% (95% CI 80.2–92.8), respectively. 52.5% of patients had grade 3 or higher treatment-emergent adverse events (TEAEs). Anlotinib in combination with continuation of EGFR-TKIs prolonged the clinical benefit of EGFR-TKIs, demonstrating favorable survival outcomes and manageable toxicity in NSCLC treated with EGFR-TKIs and had specific progression modes, such as gradual progression. NCT04007835.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"9 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929092","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":"Impact of circulating lymphoma cells at diagnosis on outcomes in patients with newly diagnosed de novo diffuse large B-cell lymphoma","authors":"Sayan Mullick Chowdhury, Subodh Bhatta, Timothy J. Voorhees, Kaitlin Annunzio, David A. Bond, Yazeed Sawalha, Audrey Sigmund, Walter Hanel, Lalit Sehgal, Lapo Alinari, Robert Baiocchi, Kami Maddocks, Beth Christian, Dan Jones, Narendranath Epperla","doi":"10.1186/s13045-024-01658-y","DOIUrl":"https://doi.org/10.1186/s13045-024-01658-y","url":null,"abstract":"Diffuse large B-cell lymphoma (DLBCL), the most common B-cell non-Hodgkin lymphoma rarely presents with circulating lymphoma cells (CL) at diagnosis. Previous studies were limited by small sample size precluding robust analysis. Hence, we evaluated the prognostic relevance of CL cells in newly diagnosed DLBCL patients. Based on peripheral blood (PB) immunophenotyping, patients were grouped into CL + and CL−. CL was defined as detectable clonally restricted B-cells that matched the actual or expected B-cell immunophenotype of DLBCL. The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall survival (OS) and diagnosis-to-treatment interval (DTI). Among the 1266 patients with DLBCL, 621 had PB flow at diagnosis, and after excluding patients not meeting eligibility criteria, 588 cases remained. Among these, 85 (15%) were CL + and 503 were CL- (85%). Patients in CL + group were younger (67 vs. 70 years, p = 0.03) with a higher proportion of non-bulky disease (85% vs. 56%, p < 0.0001), normal albumin (79% vs. 54%, p < 0.0001), and MYC/BCL2 and/or BCL6 rearrangements (18% vs. 7%, p = 0.003) compared to the CL − group. Patients with CL at diagnosis had significantly inferior PFS and OS compared with those without CL. After adjusting for factors associated with inferior PFS and OS in univariable analysis, presence of CL remained significantly associated with inferior PFS (HR = 2.04, 95%CI = 1.47–2.84, p < 0.0001) and OS (HR = 1.61, 95%CI = 1.1–2.36, p = 0.01), respectively. There was no significant difference in DTI between the two groups. Given the prognostic relevance associated with presence of CL, clinicians should consider checking PB flow at diagnosis in all newly diagnosed DLBCL patients.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"24 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929090","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":"D-ribose-5-phosphate inactivates YAP and functions as a metabolic checkpoint","authors":"Cheng-E Tu, Yong-Feng Liu, Hong-Wei Liu, Chun-Mei Jiao, Quentin Liu, Mien-Chie Hung, Peng Li, Xiang-Bo Wan, Xin-Juan Fan, Yun-Long Wang","doi":"10.1186/s13045-024-01655-1","DOIUrl":"https://doi.org/10.1186/s13045-024-01655-1","url":null,"abstract":"Targeting glucose uptake by glucose transporter (GLUT) inhibitors is a therapeutic opportunity, but efforts on GLUT inhibitors have not been successful in the clinic and the underlying mechanism remains unclear. We aim to identify the key metabolic changes responsible for cancer cell survival from glucose limitation and elucidate its mechanism. The level of phosphorylated YAP was analyzed with Western blotting and Phos-tag immunoblotting. Glucose limitation-induced metabolic changes were analyzed using targeted metabolomics (600MRM). The anti-cancer role of metabolite was examined using colony formation assay and APCmin/+ mice. Co-immunoprecipitation, LS-MS, qRT-PCR, and immunofluorescence were performed to explore the underlying mechanisms. We found that D-Ribose-5-phosphate (D5P), a product of the pentose phosphate pathway connecting glucose metabolism and nucleotide metabolism, functions as a metabolic checkpoint to activate YAP under glucose limitation to promote cancer cell survival. Mechanistically, in glucose-deprived cancer cells, D5P is decreased, which facilitates the interaction between MYH9 and LATS1, resulting in MYH9-mediated LATS1 aggregation, degradation, and further YAP activation. Interestingly, activated YAP further promotes purine nucleoside phosphorylase (PNP)-mediated breakdown of purine nucleoside to restore D5P in a feedback manner. Importantly, D5P synergistically enhances the tumor-suppressive effect of GLUT inhibitors and inhibits cancer progression in mice. Our study identifies D5P as a metabolic checkpoint linking glucose limitation stress and YAP activation, indicating that D5P may be a potential anti-cancer metabolite by enhancing glucose limitation sensitivity.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"98 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925116","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":"Dual inhibition of LAG-3 and PD-1 with IBI110 and sintilimab in advanced solid tumors: the first-in-human phase Ia/Ib study","authors":"Chenyu Mao, Anwen Xiong, Jiong Qian, Wenxiang Wang, Ying Liu, Tao Zhang, Zhihai Wu, Haiqing Ni, Jia Lu, Sixiang Long, Li Zhao, Yuling Chen, Caicun Zhou, Nong Xu","doi":"10.1186/s13045-024-01651-5","DOIUrl":"https://doi.org/10.1186/s13045-024-01651-5","url":null,"abstract":"Co-inhibition of immune checkpoints lymphocyte-activation gene 3 (LAG-3) and PD-1 is believed to enhance cancer immunotherapy through synergistic effects. Herein, we evaluate the safety and efficacy of IBI110 (anti-LAG-3 antibody) with sintilimab (an anti-PD-1 antibody) in Chinese patients with advanced solid tumors. In this open-label phase I study, phase Ia dose escalation of IBI110 monotherapy and phase Ib combination dose escalation of IBI110 plus sintilimab were conducted in patients with advanced solid tumors. Additionally, phase Ib combination dose expansion of IBI110 plus sintilimab and chemotherapy was conducted in previously untreated, advanced squamous non-small cell lung cancer (sqNSCLC) and HER-2 negative gastric cancer (GC). In phase Ia dose escalation, patients received IBI110 monotherapy at 0.01/0.1/0.3/1/3/10/20 mg/kg Q3W. In phase Ib dose escalation, patients received IBI110 at 0.3/0.7/1.5/3/5/8/10 mg/kg Q3W plus sintilimab 200 mg Q3W. In phase Ib combination dose expansion, patients received IBI110 at recommended phase 2 dose (RP2D) plus sintilimab 200 mg Q3W and chemotherapy. The primary endpoints were safety, tolerability and efficacy including objective response rate (ORR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS) assessed by RECIST v1.1 and overall survival (OS). The secondary endpoints included pharmacokinetics, pharmacodynamics and immunogenicity. In phase Ia dose escalation (n = 28), treatment-related adverse events (TRAEs) occurred in 67.9% patients and grade ≥ 3 TRAEs occurred in 21.4% patients. In phase Ib combination dose escalation (n = 45), TRAEs occurred in 75.6% patients and grade ≥ 3 TRAEs occurred in 22.2% patients. No dose-limiting toxicity (DLT) was observed. The most common TRAE was anemia (17.9%, including 3.6% ≥ G3) in phase Ia dose escalation of IBI110 monotherapy (n = 28), aspartate aminotransferase increased (28.9%, all G1-G2) in phase Ib dose escalation of IBI110 plus sintilimab (n = 45), anemia (70.0%, all G1-G2) in phase Ib dose expansion in sqNSCLC (n = 20), and neutrophil count decreased (64.7%, including 17.6%≥ G3) in phase Ib dose expansion in GC (n = 17). The RP2D of IBI110 was determined at 200 mg (3 mg/kg) Q3W. ORR in phase Ia/Ib dose escalation was 3.6% with IBI110 monotherapy and 14% with IBI110 plus sintilimab. In phase Ib combination dose expansion of IBI110 plus sintilimab and chemotherapy, unconfirmed and confirmed ORR in sqNSCLC (n = 20) was 80.0% (95% CI, 56.3–94.3) and 75.0% (95% CI, 50.9–91.3), respectively and in GC (n = 17) was 88.2% (95% CI, 63.6–98.5) and 70.6% (95% CI, 44.0-89.7), respectively. IBI110 monotherapy and in combination with sintilimab were well-tolerated in Chinese patients with advanced solid tumors. Encouraging efficacy of IBI110 in combination with sintilimab and chemotherapies was observed in sqNSCLC and GC. ClinicalTrials.gov Identifier: NCT04085185.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"65 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142904994","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":"Current and future immunotherapy for breast cancer","authors":"Natalie K. Heater, Surbhi Warrior, Janice Lu","doi":"10.1186/s13045-024-01649-z","DOIUrl":"https://doi.org/10.1186/s13045-024-01649-z","url":null,"abstract":"Substantial therapeutic advancement has been made in the field of immunotherapy in breast cancer. The immune checkpoint inhibitor pembrolizumab in combination with chemotherapy received FDA approval for both PD-L1 positive metastatic and early-stage triple-negative breast cancer, while ongoing clinical trials seek to expand the current treatment landscape for immune checkpoint inhibitors in hormone receptor positive and HER2 positive breast cancer. Antibody drug conjugates are FDA approved for triple negative and HER2+ disease, and are being studied in combination with immune checkpoint inhibitors. Vaccines and bispecific antibodies are areas of active research. Studies of cellular therapies such as tumor infiltrating lymphocytes, chimeric antigen receptor-T cells and T cell receptor engineered cells are promising and ongoing. This review provides an update of recent major clinical trials of immunotherapy in breast cancer and discusses future directions in the treatment of breast cancer.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"31 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886913","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":"Lenvatinib and immune-checkpoint inhibitors in hepatocellular carcinoma: mechanistic insights, clinical efficacy, and future perspectives","authors":"Yuhang Chen, Suoyi Dai, Chien-shan Cheng, Lianyu Chen","doi":"10.1186/s13045-024-01647-1","DOIUrl":"https://doi.org/10.1186/s13045-024-01647-1","url":null,"abstract":"Lenvatinib is a multi-target tyrosine kinase inhibitor widely used in the treatment of hepatocellular carcinoma (HCC). Its primary mechanism of action involves inhibiting signal pathways such as vascular endothelial growth factor receptors (VEGFR) and fibroblast growth factor receptors (FGFR), thereby reducing tumor cell proliferation and angiogenesis and affecting the tumor’s immune microenvironment. In the treatment of liver cancer, although lenvatinib monotherapy has shown good clinical effect, the problem of drug resistance is becoming more and more serious. This resistance may be caused by a variety of factors, including genetic mutations, signaling pathway remodeling, and changes in the tumor microenvironment. In order to overcome drug resistance, the combination of lenvatinib and other therapeutic strategies has gradually become a research hotspot, and it is worth noting that the combination of lenvatinib and immune checkpoint inhibitors (ICIs) has shown a good application prospect. This combination not only enhances the anti-tumor immune response but also helps improve therapeutic efficacy. However, combination therapy also faces challenges regarding safety and tolerability. Therefore, studying the mechanisms of resistance and identifying relevant biomarkers is particularly important, as it aids in early diagnosis and personalized treatment. This article reviews the mechanisms of lenvatinib in treating liver cancer, the mechanisms and efficacy of its combination with immune checkpoint inhibitors, the causes of resistance, the exploration of biomarkers, and other novel combination therapy strategies for lenvatinib. We hope to provide insights into the use and research of lenvatinib in clinical and scientific settings, offering new strategies for the treatment of liver cancer.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"2 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Non-invasive diagnosis of esophageal cancer by a simplified circulating cell-free DNA methylation assay targeting OTOP2 and KCNA3: a double-blinded, multicenter, prospective study","authors":"Yan Bian, Ye Gao, Han Lin, Chang Sun, Wei Wang, Siyu Sun, Xiuling Li, Zhijie Feng, Jianlin Ren, Hezhong Chen, Chaojing Lu, Jinfang Xu, Jun Zhou, Kangkang Wan, Lei Xin, Zhaoshen Li, Luowei Wang","doi":"10.1186/s13045-024-01653-3","DOIUrl":"https://doi.org/10.1186/s13045-024-01653-3","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Correction : Journal of Hematology &amp; Oncology (2024) 17:47&lt;/b&gt; &lt;b&gt;https://doi.org/10.1186/s13045-024-01565-2&lt;/b&gt;&lt;/p&gt;&lt;p&gt;The original article erroneously presents a duplicate of Figure 2A over Figure 2B. The corrected Figure 2 with correct Figure 2B can be viewed ahead in this Correction article.&lt;/p&gt;&lt;figure&gt;&lt;figcaption&gt;&lt;b data-test=\"figure-caption-text\"&gt;Fig. 2&lt;/b&gt;&lt;/figcaption&gt;&lt;picture&gt;&lt;source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13045-024-01653-3/MediaObjects/13045_2024_1653_Fig2_HTML.png?as=webp\" type=\"image/webp\"/&gt;&lt;img alt=\"figure 2\" aria-describedby=\"Fig2\" height=\"936\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13045-024-01653-3/MediaObjects/13045_2024_1653_Fig2_HTML.png\" width=\"685\"/&gt;&lt;/picture&gt;&lt;p&gt;&lt;b&gt;A&lt;/b&gt; Ct values of plasma methylated OTOP2 for the participants. &lt;b&gt;B&lt;/b&gt; Ct values of plasma methylated KCNA3 for the participants. &lt;b&gt;C&lt;/b&gt; ROC for OTOP2, KCNA3, or either for all patients with EC versus all controls. &lt;b&gt;D&lt;/b&gt; ROC for OTOP2, KCNA3, or either for patients with HGIN versus all controls. &lt;b&gt;E&lt;/b&gt; ROC for OTOP2, KCNA3, or either for patients with stage I EC versus all controls. &lt;b&gt;F&lt;/b&gt; ROC for OTOP2, KCNA3, or either for patients with stage II EC versus all controls. &lt;b&gt;G&lt;/b&gt; ROC for OTOP2, KCNA3, or either for patients with stage III EC versus all controls. &lt;b&gt;H&lt;/b&gt; ROC for OTOP2, KCNA3, or either for patients with stage IV EC versus all controls. &lt;b&gt;I&lt;/b&gt; The proportion of positive results for OTOP2, KCNA3, or either, in all patients with EC and patients with HGIN, stage I, stage II, stage III, and stage IV EC. &lt;b&gt;J&lt;/b&gt; The proportion of positive results for OTOP2, KCNA3, or either, in all controls, HC, and patients with BL, DSM, and non-DSM. Either of KCNA3 and OTOP2 positive was defined as positive, and both negative was defined as negative. &lt;b&gt;K&lt;/b&gt; Ct value of plasma methylated OTOP2 in patients with EC before and one day after surgery. &lt;b&gt;L&lt;/b&gt; Ct value of plasma methylated KCNA3 in patients with EC before and one day after surgery. &lt;b&gt;M&lt;/b&gt; Annular heatmap of the result of combining OTOP2 and KCNA3 in paired plasma samples from before and one day after surgery from the same patients with EC. Black horizontal lines are median and error bars are interquartile range. Ct = cycle threshold. ROC = the receiver operating characteristics curve. EC = esophageal cancer. ESCC = esophageal squamous cell carcinoma. EAC = esophageal adenocarcinoma. HGIN = high-grade intraepithelial neoplasia. HC = healthy control. BL = benign lesion. DSM = digestive system malignancy. P = patient&lt;/p&gt;&lt;span&gt;Full size image&lt;/span&gt;&lt;svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"&gt;&lt;use xlink:href=\"#icon-eds-i-chevron-right-small\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;/use&gt;&lt;/svg&gt;&lt;/figure&gt;&lt;span&gt;Author notes&lt;/span&gt;&lt;ol&gt;&lt;li&gt;&lt;p&gt;Yan Bian, Ye Gao, Han Lin and Chang Sun contributed equally to this work.&lt;/p&gt;&lt;/li&gt;&lt;/ol&gt;&lt;h3&gt;Authors and Affili","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"12 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866969","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":"Asciminib add-on to imatinib demonstrates sustained high rates of ongoing therapy and deep molecular responses with prolonged follow-up in the ASC4MORE study","authors":"Timothy P. Hughes, Giuseppe Saglio, Jan Geissler, Dong-Wook Kim, Elza Lomaia, Jiri Mayer, Anna Turkina, Shruti Kapoor, Ana Paula Cardoso, Becki Nieman, Sara Quenet, Jorge E. Cortes","doi":"10.1186/s13045-024-01642-6","DOIUrl":"https://doi.org/10.1186/s13045-024-01642-6","url":null,"abstract":"Up to 65% of patients with chronic myeloid leukemia (CML) who are treated with imatinib do not achieve sustained deep molecular response, which is required to attempt treatment-free remission. Asciminib is the only approved BCR::ABL1 inhibitor that Specifically Targets the ABL Myristoyl Pocket. This unique mechanism of action allows asciminib to be combined with adenosine triphosphate–competitive tyrosine kinase inhibitors to prevent resistance and enhance efficacy. The phase II ASC4MORE trial investigated the strategy of adding asciminib to imatinib in patients who have not achieved deep molecular response with imatinib. In ASC4MORE, 84 patients with CML in chronic phase not achieving deep molecular response after ≥ 1 year of imatinib therapy were randomized to asciminib 40 or 60 mg once daily (QD) add-on to imatinib 400 mg QD, continued imatinib 400 mg QD, or switch to nilotinib 300 mg twice daily. More patients in the asciminib 40- and 60-mg QD add-on arms (19.0% and 28.6%, respectively) achieved MR4.5 (BCR::ABL1 ≤ 0.0032% on the International Scale) at week 48 (primary endpoint) than patients in the continued imatinib (0.0%) and switch to nilotinib (4.8%) arms. Fewer patients discontinued asciminib 40- and 60-mg QD add-on treatment (14.3% and 23.8%, respectively) than imatinib (76.2%, including crossover patients) and nilotinib (47.6%). Asciminib add-on was tolerable, with rates of AEs and AEs leading to discontinuation less than those with nilotinib, although higher than those with continued imatinib (as expected in these patients who had already been tolerating imatinib for ≥ 1 year). No new or worsening safety signals were observed with asciminib add-on vs the known asciminib monotherapy safety profile. Overall, these results support asciminib add-on as a treatment strategy to help patients with CML in chronic phase stay on therapy to safely achieve rapid and deep response, although further investigation is needed before this strategy is incorporated into clinical practice. NCT03578367","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"22 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848831","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}