The investigators aim to perform a randomized clinical trial to determine the optimal timing of hepatitis B vaccination after hematopoietic cell transplantation (HCT) through evaluating the immunity effect of two different vaccination schedules (initiated at 3 or 6 months after transplantation) in patients with different immune reconstitution status.

开始日期2025-06-01

申办/合作机构

中国医学科学院血液病医院

NCT06880354

/ Not yet recruiting临床1期IIT

A Clinical Study to Evaluate the Safety and Efficacy of CLL1 and CD38 Dual-Target CAR-T Cell Injection in the Treatment of Relapsed or Refractory Acute Myeloid Leukemia

This is a single-arm, open-label, phase I dose-escalation clinical study to evaluate the safety and preliminary efficacy of CLL1 and CD38 dual-target CAR T cell injection in r/r AML subjects.

开始日期2025-03-31

申办/合作机构

中国医学科学院血液病医院

[+2]

ChiCTR2500099017

/ SuspendedN/AIIT

Clinical study of umbilical cord blood mononuclear cells (UCB-MNCs) for the treatment of refractory intestinal aGVHD in

开始日期2025-03-20

申办/合作机构

中国医学科学院血液病医院

100 项与中国医学科学院血液病医院相关的临床结果

登录后查看更多信息

0 项与中国医学科学院血液病医院相关的专利（医药）

登录后查看更多信息

593

项与中国医学科学院血液病医院相关的文献（医药）

2023-11-02·Blood

IST Combined with Full-Dose Rhtpo in the Treatment of Severe Aplastic Anemia -a Prospective Single-Center Clinical Study

作者: Hu, Jing ; Zhang, Fengkui ; Zhang, Li ; Yang, Wenrui ; Zhou, Kang ; Zhao, Xin ; Fan, Huihui ; Xiong, Youzhen ; Jing, Liping

BACKGROUND: Immunosuppressive therapy (IST) (anti-thymocyte immunoglobulin (ATG) and cyclosporine (CSA)) is the treatment of choice for patients with acquired severe aplastic anemia (SAA) who are ineligible for hematopoietic stem cell transplantation (HSCT), which results in a hematological response (HR) in about 60-70% of SAA patients, while 1/3 of patients fail to achieve a hematological response. TPO is a hepatic-secreted hematopoietic growth factor that specifically regulates platelet production, induces hematopoietic stem cell differentiation to megakaryocytes by binding to the TPO receptor (MPL), stimulates megakaryocyte proliferation and differentiation, and promotes platelet production and release. Previous retrospective studies have demonstrated that IST combined with rhTPO improves the early hematologic response in SAA patients, but efficacy reported by centers varied depending on the dose and duration of rhTPO. There are no prospective studies of rhTPO application in SAA to confirm its efficacy. So this study was designed to observe the early feeicacy and safety of the SAA patients who were treated with IST combination with full-dose rhTPO.METHODS: This study was a single-center, single-arm, prospective cohort clinical study, enrolling 33 naive SAA patients aged between 14-70 years who diagnosed after April 2021 in our study center. The patients treated with IST combined with full-dose rhTPO (300U/kg.d) for 8 weeks starting from the first day of ATG. The primary endpoint of the observational study protocol good response rate, blood product transfusion volume and safety profile at 3 months of treatment of initial SAA. The patients were also evaluated for total hematologic response rate and adverse effects of drug application, clonal shift rate, and recurrence rate at 3 and 6 months after treatment.Efficacy Criteria：Complete response (CR): HGB>100 g/L, PLT> 100×10 9/L and ANC>1.5×10 9/L; ② Good partial response (GPR): HGB>80g/L, PLT> 50×10 9/L and ANC>1.0×10 9/L; ③ Partial response (PR): withdrawal from blood product transfusion dependence (HGB>70g/L, PLT> 20×10 9/L), hematologic tests improved and no longer met the SAA criteria, but blood count did not meet the GPR criteria. ④No response to treatment (NR): Continuous transfusion dependency was classified as no response. and/or blood count still met SAA criteria. We defined CR+GPR+PR as HR and CR+GPR as good HR.RESULTS: The rhTPO group enrolled 33 patients, and the control group was 99 patients who applied the caliper value of 0.2 to match the previous unapplied TPO treatment of SAA. At 3 months after IST treatment efficacy, the HR rate of 33 patients in the rhTPO group was 66.67% (22 /33 ), and the rate of good HR was 36.4% (12/33). The HR rate in the control group was 32.32% (32 /99 ), and the rate of good HR was 12.12% (12/99). The HR rate and the good HR rate between the two group were significantly statistical differences (66.67% v 32.32%; 36.4% v 12.12%), (P value=0.001; 0.002). At 6 months after IST treatment, the HR rate and good HR rate in the rhTPO group had a significantly higher than those of the control group (66.67% v 32.32%; 36.4% v 12.12%), (P value=0.001; 0.002).No disease transformation such as myelofibrosis, myelodysplastic syndrome and acute myeloid leukemia occurred in all enrolled patients during the follow-up period.CONCLUSION: 22 of the 33 SAA patients in this study achieved HR at 3 months after IST treatment, including 36.4% cases achived good HR , which is the highest good efficacy response in a prospective study of SAA patients in China known to us to date. This confirms that full-dose rhTPO, as a macromolecular peptide, can also promote the recovery of bone marrow hematopoietic function, significantly improved the rapidity and strength of HR in SAA patients. And its clinical effect is no less than that of the various TPO-Ras that have been widely used so far, and may even be higher.【Keywords】severe aplastic anemia; recombinant human thrombopoietin; immunosuppression treatment.

2023-11-02·Blood

Quantum-First Trial: FMS-like Tyrosine Kinase 3-Internal Tandem Duplication ( FLT3-ITD)-Specific Measurable Residual Disease (MRD) Clearance Assessed through Induction (IND) and Consolidation (CONS) Is Associated with Improved Overall Survival (OS) in Newly Diagnosed (nd) FLT3-ITD+ AML Patients (pts)

作者: Montesinos, Pau ; Cortes, Jorge ; Erba, Harry P. ; Amadori, Sergio ; Sekeres, Mikkael A. ; Kim, Heeje ; Vrhovac, Radovan ; Liu, Li ; Schlenk, Richard F ; Wang, Jianxiang ; Dombret, Hervé ; Imadalou, Karima ; Levis, Mark J. ; Perl, Alexander ; Zak, Pavel ; Lesegretain, Arnaud ; Wang, Po-Nan ; Chang, Ken C N ; Rohrbach, Jaime E ; Kamel, Yasser Mostafa ; Patkowska, Elzbieta

BackgroundDetection of MRD by flow cytometry or gene fusion transcript quantitation increasingly is used to guide treatment decisions in AML. Molecular monitoring of recurrent gene mutations for MRD detection is an alternative strategy but, other than for nucleophosmin 1 ( NPM1) gene quantitation, remains controversial. FLT3-ITD is among the most common recurrent mutations in AML and confers a worse prognosis vs FLT3-wild-type and FLT3-TKD+ AML. Routine use of FLT3-ITD detection in remission as a predictor of relapse risk or OS has been limited by the low sensitivity of both conventional PCR-based detection methods and broad NGS platforms in clinical practice settings. More recently, FLT3-ITD-specific PCR-NGS assays such as getITD (PMID: 31089248) show greater sensitivity and ease of interpretation that point to eventual routine clinical application. However, the clinical value of these measurements has not been evaluated prospectively in large scale randomized controlled trials of FLT3 inhibitors. The phase 3 QuANTUM-First study (NCT02668653) evaluated the novel, potent, and highly selective type II FLT3 inhibitor quizartinib (Quiz) in nd FLT3-ITD+ AML pts and demonstrated that Quiz added to intensive IND and CONS, ± transplant, followed by single-agent continuation (CONT) therapy (Tx) resulted in a significant improvement in OS (PMID: 37116523). We analyzed if FLT3-ITD-specific MRD in QuANTUM-First pts impacted the clinical outcome or the benefits provided by Quiz in nd FLT3-ITD+ AML pts.MethodsGenomic DNA, isolated from bone marrow aspirates or peripheral blood from pts after achievement of remission after 1 or 2 courses of IND and at end of CONS (prior to transplant or CONT cycle 1 day 1 [C1D1] for transplant pts and prior to CONT C1D1 for non-transplant pts), was analyzed with a FLT3-ITD PCR-NGS assay specifically developed for this trial (PMID: 31722002). ITD mutations detected after IND were cross-validated against the ITD detected at enrollment for each patient. Using a custom bioinformatics program, ITD mutations were identified, and variant allele frequencies (VAFs) were calculated with a sensitivity of 10 −5. MRD was classified as undetectable (using the 0 cutoff) or detectable above or below a 10 −4 predefined cutoff (based on lower limit of quantification for the assay). Comparisons of complete response (CR), composite complete response (CRc=CR+CRi), and the rate of pts achieving CRc during IND with no MRD between arms were made using a stratified Cochran-Mantel-Haenszel test. Comparison of FLT3-ITD VAF during IND and during CONS between arms was made using Wilcoxon rank sum test. All P-values were not adjusted for multiplicity.ResultsIn QuANTUM-First, 539 nd FLT3-ITD+ AML pts were randomized to Quiz (n=268) or placebo (PBO; n=271). Of the 539 randomized pts, 368 (68.3%) achieved CRc after 1 or 2 courses of IND, and MRD analysis was performed on 321 (87.2%) of these pts (162 pts in Quiz and 159 pts in PBO) using samples collected at the time of response assessment during IND, before further Tx. MRD was also assessed in 337 pts (172 pts in Quiz and 165 pts in PBO) by end of up to 4 cycles of CONS prior to CONT/maintenance Tx. Of these pts, 166 additionally received transplant (87 in Quiz, 79 in PBO). The % of pts in CRc at end of IND with FLT3-ITD MRD of <10 −4 was similar between study arms (25.4% Quiz vs 21.8% PBO, nominal P = 0.3430), however, a greater % of pts in CRc had undetectable MRD with Quiz than PBO (12.3% vs 7.0%, nominal P = 0.0403). Among pts with CRc at end of IND, the median best FLT3-ITD VAF by end of CONS was lower (0% versus 0.0017%; nominal P = 0.0006) with Quiz vs PBO (Fig 1) and, using the 0 cutoff at end of IND, a longer OS was observed with Quiz vs PBO, regardless of MRD status, with a greater effect with Quiz (HR, 0.789 in MRD− pts; HR, 0.749 in MRD+ pts; Fig 2). In MRD+ pts, the median OS was not reached with Quiz and 35.4 months with PBO (Fig 2). Performing this analysis with an MRD cutoff of 10 ‒4 yielded similar findings (HR, 0.696 in MRD− pts; HR, 0.800 in MRD+ pts). Additional data about MRD impact on pts ± transplant in this trial will be presented.ConclusionsThese findings demonstrate the potential prognostic utility of FLT3-ITD-specific MRD measurements in the clinical management of pts with FLT3-ITD+ AML. Our data suggest that long-term OS benefits conferred by Quiz in part derive from a deep and sustained reduction of the FLT3-ITD+ leukemia burden.

2023-11-02·Blood

Recipient Resident Macrophage Plays a Crucial Role in Acute Graft-Versus-Host-Disease after Allogeneic Stem Cell Transplantation By Regulation of Damage-Associated Molecular Pattern Phagocytosis

作者: Shen, Yuyan ; Feng, Sizhou ; Zhang, Tingting ; Jiang, Erlie ; Liao, Xudong ; Chen, Zhangjie ; Wang, Jieru ; Zhen, Sisi

IntroductionEvidence shows allogeneic hematopoietic stem cell transplantation (alloHSCT) provides life-sustaining therapy for many hematologic malignancies. Unfortunately, in many cases it is complicated by acute-graft-versus-host disease (aGVHD), a life-threatening sequela. Most interstitial tissues contain populations of resident macrophages. Multiple studies have investigated the role of infiltrating macrophages in aGVHD, but little is known about the role of resident macrophage in aGVHD. To address this issue, we adopt a LysM cre/cre-Hif1a flox/flox mice (KO)as host mice with abnormal macrophage whose host resident macrophage remains unchanged early after allo-HSCT. KO mice received alloHSCT after Total body irradiation (TBI) from wild-type(WT) mice of BALB/c background. The neutrophil and circulating monocyte/macrophage were replaced by WT cells and the resident macrophage remains unchanged after this procedure. The grade of aGVHD and survival was observed.MethodsRecipient mice are on the background of C57BL/6(H-2 b), and donor mice are wild-type BALB/c (H-2 d ) mice. All mice used were 8-12 week old. All animal experiment protocols were approved. LysM cre/cre (CRE) mice were taken as control recipients. Mice were exposed to TBI split into two doses separated by 4h. KO and CRE C57/BL mice received 9 Gy TBI. 18h after irradiation, mice of two groups were injected i.v with 1×10 7BM cells and 1.5×10 7 splenocytes isolated from WT BALB/c mice. aGVHD score and survival are monitored daily. Isolation of Kupffer subsets was performed as CD45 +CD11b + Ly6G -F4/80 +, which from KO and CRE mice of GVHD model were taken to do single-cell sequencing assay. Survival curves were plotted by the Kaplan-Meier method. The statistical significance between group means was determined using t-test by Graphpad prism9.5. The level of significance was set at P<0.05.ResultsThe mean survival of KO mice is 18.6 days (95%CI 14.06-22.6) post alloHSCT, while the mean survival of control mice is 37.6 days (95%CI 29.7-45.6)(n=8)( P <0.001). Weight loss (% of baseline weight on the day of TBI) starts to differ on day 14 post-HSCT, with the KO group of 101.7 and Control group of 84.9 ( P <0.05). GVHD score starts to differ on day 10 post-HSCT, with the KO group of mean score 5.1 and control group 3.9 ( P <0.05)(n=8) (Figure1). The GVHD score remains statistically different till day 24 post-HSCT. On day 24, all KO mice die while one control mouse live up to 58 days. The liver function presented by ALT is different on day 14 post-HSCT, KO group with mean ALT 209.0 U/L is higher than Control group whose mean ALT is 64.9U/L(n=4). On day 21, Liver GVHD pathology score of the KO group is 7, compared to 5.2 of the control group(n=6)( P<0.05). Thus, KO mice present with a more severe aGVHD phenotype than CRE mice. Macrophage is known to have deficient phagocytosis ability when lacking Hif1-a, which is also confirmed through phagocytosis assay in our lab by FITC marked particles based on melamine resin ( P <0.05). We hypothesize the disability of phagocytosis of recipient resident macrophage renders more DNA debris (also known as DAMP) generated from conditioning, leading to susceptibility of aGVHD, we applied Dnase I to mice from day4 to day14 post-HSCT. The survival of KO mice after injection of Dnase I, with a mean survival of 39.9 days, is better than KO mice with vehicle injection ( P <0.05). After Dnase I injection, KO group, compared to 63.5 days mean survival of the control group, there is no statistical difference ( P=0.113). In order to look into more mechanisms, CD45 + cells from the liver of KO and CRE mice with GVHD model 21 days post-HSCT were isolated to do single-cell sequencing. KO mice revealed more T cell ratio than CRE mice. GO analysis revealed several abnormalities including regulation of lymphocyte activation.ConclusionsWe build GVHD model on LysM cre/cre-Hif1a flox/flox and LysM cre/cre mice, both adopt alloHSCT from wild-type BALB/c mice. After HSCT, both groups are replaced with wild-type neutrophils and circulating monocyte/macrophages, leaving resident macrophages different. KO mice present with exacerbated GVHD phenotype than CRE mice after alloHSCT. This difference could be mitigated by Dnase I injection. Thus, the resident macrophage of the recipient plays a crucial role in aGVHD occurrence, which is partly by regulation of DAMP phagocytosis.

191

项与中国医学科学院血液病医院相关的新闻（医药）

2025-04-30

·辉瑞制药

靶向免疫疗法易瑞欧®（埃纳妥单抗）首处落地，深度缓解实现多发性骨髓瘤患者“更长生存”

埃纳妥单抗是一款皮下注射、固定剂量的双特异性抗体药物，患者在接受24周每周一次给药治疗后，可选择每2周一次给药的长期治疗方式今日，辉瑞旗下治疗多发性骨髓瘤的靶向免疫疗法易瑞欧®（埃纳妥单抗）在北京、天津、广州、哈尔滨等地多家医院开出全国首日处方，标志着这一靶向BCMA/CD3的双特异性抗体药物正式惠及我国患者，为既往接受过多线治疗的复发或难治性多发性骨髓瘤（RRMM）成人患者带来全新的治疗选择。埃纳妥单抗是一款皮下注射、固定剂量的双特异性抗体药物，通过同时结合骨髓瘤细胞表面的B细胞成熟抗原（BCMA）和T细胞表面的CD3，激活T细胞靶向清除肿瘤细胞，助力患者延长生存期、改善预后。✦左右滑动查看✦埃纳妥单抗全国首日处方易达深控：创新药物带来RRMM治疗新希望多发性骨髓瘤（MM）是一种克隆性浆细胞异常增殖的恶性疾病，是全球第二高发的血液系统恶性肿瘤，全球每年约有188000人被诊断出患有多发性骨髓瘤1。约40%的确诊患者生存期不足五年2。数据显示，2022年，我国约有30300例MM新发病例和18662例MM死亡病例3。在治疗过程中，绝大多数患者会出现复发或耐药，进入复发难治阶段，临床治疗面临巨大挑战。马军教授中国临床肿瘤学会（CSCO）监事会监事长、哈尔滨血液病肿瘤研究所所长近年来多发性骨髓瘤的治疗手段不断丰富，但在经历三线及以上治疗后，患者面临的复发与耐药问题依然严峻，治疗选择极其有限。对于他们而言，时间就是生命。埃纳妥单抗作为一款创新的靶向BCMA/CD3的双特异性抗体药物，为高度耐药的患者群体带来了新的治疗希望。我们期待这类创新疗法在中国的落地能够为患者带来切实的生存获益。真实世界研究显示：三重暴露（接受过≥1种蛋白酶体抑制剂、免疫调节剂和抗CD38单抗）的复发或难治性多发性骨髓瘤（RRMM）患者数量在2016-2020年间增加了近8倍4。这部分患者群体的预后极差，客观缓解率（ORR）31.9%，中位无进展生存期(mPFS)仅4.6个月，中位总生存期（mOS）仅13.8个月5。邱录贵教授中国临床肿瘤学会（CSCO）骨髓瘤专家委员会主任委员、中国医学科学院血液病医院首席顾问专家随着蛋白酶体抑制剂、免疫调节剂以及CD38单抗的广泛应用，三重暴露的多发性骨髓瘤患者越来越多。随着治疗线数增加，患者缓解时间逐渐缩短，治疗难度不断加大。特别是RRMM患者，在疾病进展时可供选择的治疗方案有限，采用现有常规方案治疗总生存期往往不足一年。创新机制：突破MM后线治疗困境复发加剧了MM的治疗难度，复发次数越多，治疗难度越大，患者的无进展生存期和复发后的生存时间显著缩短。复发后肿瘤细胞易发生克隆演化，通过耐药机制逃避治疗6，尤其是多线复发患者常面临蛋白酶体抑制剂、免疫调节剂、抗CD38单抗等多药耐药，导致传统方案失效。李娟教授中山大学附属第一医院血液内科面对临床困境，B细胞成熟抗原（BCMA）靶向免疫疗法正开启多发性骨髓瘤治疗的变革时代。BCMA作为肿瘤坏死因子受体（TNFR）超家族的成员在浆细胞表面表达，而在恶性浆细胞中的表达要高于正常浆细胞，且在几乎所有的MM细胞表面表达7。B细胞成熟抗原（BCMA）在恶性浆细胞表面高度表达，是突破多线耐药的MM治疗困境的理想靶点。埃纳妥单抗是一种新型人源化双特异性IgG2抗体，由两种单克隆抗体衍生而来，即抗BCMA单克隆抗体和抗CD3单克隆抗体。它能与骨髓瘤细胞上的BCMA和T细胞上的CD3结合，从而激活T细胞杀死骨髓瘤细胞。路瑾教授北京大学人民医院血液病研究所作为靶向BCMA的双特异性抗体药物，埃纳妥单抗在三种药物暴露后的RRMM患者中展现出了深度且持久的疗效，中位无进展生存期是目前同类产品中最长的，总体生存数据令人鼓舞，有望帮助患者获得深度持久的缓解以及更长的无进展生存期。长焕新生：助力患者多维获益对于多线复发的MM患者，核心治疗目标是在控制疾病、减轻症状、避免重要脏器损害和提高生活质量的基础上，尽可能获得最大程度的缓解8。研究表明，缓解深度与生存期密切相关，患者的缓解深度越深，生存期越长久9。不同于传统静脉输注疗法，埃纳妥单抗为即用型溶液，固定剂量皮下注射，无需根据体重调整，可单药或联合治疗，匹配临床需求，最小化住院时间，仅剂量递增阶段需住院，24周后符合条件患者给药频率可调整为每2周一次。其简单便捷的治疗方案有助于提升患者治疗依从性，提高患者生活质量。安刚教授中国医学科学院血液病医院由于耐药性，RRMM患者在疾病进展时往往治疗选择有限，导致缓解期和缓解持续时间越来越短，面对治疗耐药性加剧与免疫应答下降的双重挑战，亟需引入机制创新、疗效确切的治疗手段。埃纳妥单抗等创新药物的出现，是我们向这一目标迈出的关键一步。希望通过创新治疗方案，使多发性骨髓瘤真正实现从‘延长生命’到‘提高生活质量’的转变，为更多患者点亮希望。2025年3月，靶向免疫疗法易瑞欧®（埃纳妥单抗）获国家药品监督管理局附条件批准，适用于既往接受过至少三线治疗（包括一种蛋白酶体抑制剂、一种免疫调节剂和一种抗CD38单克隆抗体）的复发或难治性多发性骨髓瘤成人患者的治疗。关于易瑞欧®（埃纳妥单抗）滑动阅览易瑞欧®是一种皮下注射的B细胞成熟抗原（BCMA）和CD3的双特异性抗体（BsAb）免疫疗法，它能与骨髓瘤细胞上的BCMA和T细胞上的CD3结合，激活T细胞杀死骨髓瘤细胞。基于MagnetisMM-3研究的结果，易瑞欧®在2023年8月获美国食品药品管理局加速批准，用于治疗既往接受过至少四线治疗（包括1种蛋白酶体抑制剂、1种免疫调节剂和1种抗CD38单克隆抗体）的复发或难治性多发性骨髓瘤成人患者。2023年12月，欧盟委员会已授予易瑞欧®附条件上市许可，单药用于治疗既往接受过至少三种治疗，并且末次治疗出现疾病进展的复发或难治性多发性骨髓瘤成人患者（包括1种蛋白酶体抑制剂、1种免疫调节剂和1种抗CD38单克隆抗体）。辉瑞公司正在进行广泛的MagnetisMM临床开发项目，该项目正在研究埃纳妥单抗在多发性骨髓瘤各治疗阶段中的应用，包括从复发或难治性多发性骨髓瘤到新诊断的多发性骨髓瘤。1 World Health Organization. Globocan 2020: Multiple Myeloma. Available from: https://gco.iarc.who.int/media/globocan/factsheets/cancers/35-multiple-myeloma-fact-sheet.pdf [Last accessed: August 2024].2 National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Myeloma. Available from: https://seer.cancer.gov/statfacts/html/mulmy.html [Last accessed: April 2024].3 IARC WHO. https://gco.iarc.who.int/media/globocan/factsheets/populations/160-china-fact-sheet.pdf. Accessed Aug. 20244 Delea TE, et al. Oncol Ther. 2024 Sep;12(3):565-583.5 Mateos MV, et al. Leukemia. 2024 Dec;38(12):2554-2560.6 中华医学会血液学分会浆细胞疾病学组, 中国医师协会多发性骨髓瘤专业委员会. 中国首次复发多发性骨髓瘤诊治指南（2022年版） [J] . 中华血液学杂志, 2022, 43(10) : 810-817.7 Yu B, et al. J Hematol Oncol. 2020;13:125.8 CSCO恶性血液病诊疗指南2024-多发性骨髓瘤9 Goldschmidt H, et al. Leukemia . 2020 Nov;34(11):3019-3027. 往期 · 推荐遏制耐药，拯救生命，我们在行动！生命的韧性：与多发性骨髓瘤共处辉瑞靶向免疫疗法易瑞欧®（埃纳妥单抗）在华获批，用于治疗复发或难治性多发性骨髓瘤【一键通达】药品问询不再难，医学信息解忧烦!

免疫疗法CSCO会议

2025-04-27

·求实药社

诺诚健华宜诺凯®（奥布替尼）在中国获批一线治疗慢性淋巴细胞白血病/小淋巴细胞淋巴瘤 | 项目进展

来源：新药创始人诺诚健华（上交所代码：688428；香港联交所代码：09969）近日宣布，公司自主研发的新型BTK（布鲁顿酪氨酸激酶）抑制剂奥布替尼（商品名：宜诺凯®）获得中国国家药品监督管理局（NMPA）批准，用于一线治疗慢性淋巴细胞白血病/小淋巴细胞淋巴瘤 (CLL/SLL) 。此次一线CLL/SLL的获批将惠及更多淋巴瘤患者。此前，奥布替尼已在中国获批用于治疗既往至少接受过一次治疗的CLL/SLL、套细胞淋巴瘤（R/R MCL）和边缘区淋巴瘤（R/R MZL），三项适应症均已纳入国家医保。临床试验的主要研究者江苏省人民医院李建勇教授表示：“作为我国自主研发的I类创新药，奥布替尼自2020年上市以来，已经在复发/难治性CLL/SLL等B细胞恶性肿瘤的治疗中展现了卓越的疗效和安全性，显示出更高的完全缓解率。此次获批一线治疗CLL/SLL，意味着更多淋巴瘤患者能获益这种高效、精准的治疗方案，一线治疗研究显示完全缓解率高达12.1%，将为我国血液肿瘤的治疗带来新的希望和突破。”临床试验的主要研究者中国医学科学院血液病医院邱录贵教授表示：“此项研究开展整个过程正值新冠疫情，研究启动、患者招募和管理均面对严峻的挑战，大家克服各种困难，奥布替尼一线治疗CLL/SLL依然展示了显著的疗效和良好的安全性，证实了奥布替尼的创新性。从临床研究到真实世界，奥布替尼对一些高危患者和有合并症的患者，也能提供有效的治疗选择。”哈尔滨血液病肿瘤研究所马军教授表示：“随着奥布替尼一线CLL/SLL获批以及在真实世界中的数据积累，正在为越来越多的淋巴瘤患者带来获益。与此同时，奥布替尼已被CSCO淋巴瘤诊疗指南列为CLL/SLL一线治疗的I级推荐。期待奥布替尼能够积累更广泛、更长随访的研究数据，进而指导临床实践，为更多淋巴瘤患者提供更好的治疗选择。”北京大学肿瘤医院朱军教授表示：“奥布替尼在血液肿瘤治疗中的应用前景令人瞩目，奥布替尼的高选择性、低脱靶效应等特点，使其在疗效和安全性上更具优势。相信随着奥布替尼在一线治疗中的广泛应用，将为更多患者带来生存获益，也为血液肿瘤治疗提供了新的范例。”诺诚健华联合创始人/董事长兼CEO崔霁松博士表示：“很高兴看到奥布替尼一线CLL/SLL的获批，这是公司在血液瘤领域取得的又一个重要里程碑。衷心感谢所有参与此项研究的专家、患者和公司员工的不懈努力。我们期待这一获批能为更多淋巴瘤患者带来新的希望和治疗选择，为血液肿瘤治疗注入新的活力。”奥布替尼是诺诚健华自主研发的具有高度靶标选择性的新型BTK抑制剂，可以避免脱靶相关的不良事件，改善安全性和有效性。CLL/SLL是最常见的白血病类型之一，是B淋巴细胞的一种惰性恶性肿瘤。全球每年有19.1万新确诊的CLL病例和6.1万死亡病例[1]，中国CLL/SLL的发病率呈上升趋势[2]。[1] 美国血液学杂志（American Journal of Hematology）[2] Frost & Sullivan免责声明：文章内容仅供参考，不构成投资建议。投资者据此操作，风险自担, 关于对文中陈述、观点判断保持中立，不对所包含内容的准确性、可靠性或完整性提供任何明示或暗示的保证。请读者仅作参考，并请自行承担全部。联系我们SIT 2025展位火热预定中！扫码立即咨询电话：13816031174（同微信）赞助形式包括但不仅限于演讲席位、会场展位、会刊彩页、晚宴赞助、会议用品宣传等。点击此处“阅读全文”咨询更多精彩！

CSCO会议上市批准申请上市临床申请

2025-04-27

·信达生物

CSCO 指南 | 儿童Ph+ALL（费城染色体阳性急性淋巴细胞白血病）治疗，奥雷巴替尼获CSCO指南升级推荐

转载自：CSCO会议2025版中国临床肿瘤学会（CSCO）儿童及青少年白血病诊疗指南重磅更新，在儿童Ph+ALL（费城染色体阳性急性淋巴细胞白血病）患者中，奥雷巴替尼推荐升级，其中在BCR::ABL激酶区T315I突变患者中升级为I级推荐。针对儿童Ph+ALL患者，奥雷巴替尼突破性疗效与安全性获循证支持，为临床提供关键解决方案。达沙替尼联合化疗一线治疗儿童Ph+ALL遭遇耐药难题儿童Ph+ALL（费城染色体阳性急性淋巴细胞白血病）是急性白血病中预后较差的亚型，占儿童ALL的3%-5%[1]。目前针对儿童Ph+ALL的治疗已形成以酪氨酸激酶抑制剂（TKI）联合化疗为核心的综合策略，并逐步向精准分层与靶向免疫治疗演进。TKI应用于临床以来，儿童Ph+ALL的生存率实现了从20%到60%以上的跨越式提升[2]。TKI通过特异性抑制BCR-ABL1融合蛋白的酪氨酸激酶活性，阻断下游致癌信号通路（如RAS、PI3K/AKT），从而发挥抗癌作用。2023版CSCO儿童及青少年白血病诊疗指南推荐达沙替尼联合化疗作为初治儿童Ph+ALL的一线方案（I级推荐）；BCR-ABL激酶区T315I突变患者可选择普纳替尼、奥雷巴替尼等Ⅲ代TKI（II级推荐）[3]。然而，尽管达沙替尼联合化疗应用于Ph+ALL儿童治疗取得一定效果，但仍然存在诸多未被满足的临床需求，其中达沙替尼耐药是首要临床痛点。BCR-ABL激酶区突变是Ph+ALL患者对TKI产生耐药的核心机制[4]，常见的突变包括P环突变（E255K）、激活环突变（H396P）、SH2结构区突变（M351T）和守门员突变（T315I）。其中T315I突变使得第315位苏氨酸被异亮氨酸取代，导致达沙替尼因空间位阻无法结合[5]，致使达沙替尼耐药，造成患者不良预后。有研究指出，达沙替尼耐药患者中，T315I突变占比达34.1%，为最常见的BCR-ABL激酶区突变[6]。此外，还存在强化化疗导致骨髓抑制、感染等并发症，针对儿童开展的临床试验数据缺乏等问题。同时，复发/难治病例的治疗仍然是严峻的临床挑战。CSCO指南权威认可奥雷巴替尼（耐立克®）推荐升级第三代TKI奥雷巴替尼展现出卓越的耐药突破潜力。奥雷巴替尼直接竞争性结合BCR-ABL1激酶的ATP结合位点，可有效抑制 BCR-ABL酪氨酸激酶野生型及多种突变型（T315I、E255K、G250E、H396P、M351T、Q252H、Y253F等）以及复合突变的活性[7]，显著改善因BCR-ABL激酶区突变而导致的TKI耐药[8]。因此，2025 CSCO儿童及青少年白血病诊疗指南推荐，在儿童Ph+ALL患者中，奥雷巴替尼推荐升级，其中在BCR::ABL激酶区T315I突变患者中升级为I级推荐。在此次指南更新中，奥雷巴替尼治疗儿童Ph+ALL的推荐等级得到了显著提升[9]，拓展了靶向治疗的应用范围，将丰富临床用药选择，帮助临床医生根据患者个体情况（如突变类型、治疗反应和耐受性）灵活调整TKI治疗方案。图1.2025版CSCO儿童及青少年白血病诊疗指南更新，奥雷巴替尼治疗儿童Ph+ALL推荐升级科学循证奥雷巴替尼（耐立克®）治疗儿童Ph+ALL证据不断积累近期研究显示，奥雷巴替尼在治疗复发/难治儿童Ph+ALL中，显示出良好的缓解率与安全性。在一项纳入7例复发/难治儿童Ph+ALL患者的回顾性研究中[10]，奥雷巴替尼单药或联合化疗的完全缓解率达80%，在5例可评估病例中4例达到分子学MRD阴性，且严重动脉闭塞事件发生率仅1.6%，优于同属于第三代TKI的普纳替尼；并且，1例CNSL复发患者头痛症状在用药后缓解，3例合并CNS复发的患儿脑脊液白血病细胞快速清除；同时，6例可评估患儿中仅3例出现不良反应（2级肢体疼痛、3级发热感染等），无因不良反应停药病例。该研究首次证实奥雷巴替尼在儿童复发Ph+ALL中兼具高缓解率与良好安全性，尤其对T315I突变及CNSL患者显示显著疗效。后续一项8例病例系列报告进一步验证了这一结果[11]。图2. 回顾性研究纳入的7例儿童治疗进程与血液、神经微小残留病剩余比例变化目前，奥雷巴替尼联合Bcl-2抑制剂APG-2575治疗复发/难治Ph+ALL儿童患者的前瞻性临床研究正在开展，1b期试验纳入了10例11-15岁患者（男性6例），其中90%为p190亚型，30%携带T315I/F317L耐药突变。研究采用3+3剂量递增模式，评估奥雷巴替尼联合Bcl-2抑制剂APG-2575的疗效与安全性。结果显示，联合治疗使客观缓解率（ORR）从单药阶段的33.3%显著提升至83.3%，7例可评估患者中5例（71.4%）达到MRD阴性。此外，药代动力学分析证实，儿童患者的药物暴露量与成人相当，且无显著蓄积效应（研究注册号：NCT05599237）[12]。这些数据为奥雷巴替尼在儿童Ph+ALL中的应用提供了重要循证依据，对耐药突变患者以及复发/难治患者展现出突破性疗效。专家点评竺晓凡教授竺晓凡教授中国医学科学院血液病医院医学博士、硕士生导师主任医师，博士研究生导师儿童血液病诊疗中心首席专家国务院特殊津贴专家天津市有突出贡献专家国家卫生健康委儿童白血病专家委员会副主任委员中国抗癌协会小儿肿瘤专业委员会候任主任委员天津市医学会儿科分会血液学组组长天津市小儿肿瘤专业委员会副主委《中华儿科杂志》、《中华血液学杂志》等杂志编委获国家自然科学二等奖、宋庆龄儿科医学奖、五洲女子科技奖、天津市自然科学一等奖等奖项奥雷巴替尼作为我国自主研发的第三代TKI，在儿童Ph+ALL治疗领域取得了突破性进展。2025版CSCO指南将其对T315I突变患者的推荐等级提升至I级，这一重要更新充分体现了其临床价值。从作用机制来看，奥雷巴替尼直接竞争性结合BCR::ABL1激酶的ATP结合位点，可有效抑制 BCR::ABL 酪氨酸激酶野生型及多种突变型（T315I、E255K、G250E、H396P、M351T、Q252H、 Y253F等）以及复合突变的活性。同时，临床研究数据令人振奋，在复发/难治儿童Ph+ALL中，单药或联合治疗的完全缓解率达80%，分子学缓解率显著，且对CNSL患者同样有效。未来，我们期待更多研究进一步验证其长期疗效，并探索更优化的联合治疗方案，为儿童Ph+ALL患者带来更多治愈希望。参考文献：1. Hunger SP, Mullighan CG. Acute lymphoblastic leukemia in children. N Engl J Med. 2015;373:1541-52.2. Schultz KR, Bowman WP, Aledo A, et al. Improved early event-free survival with imatinib in philadelphia chromosome-positive acute lymphoblastic leukemia: A children's oncology group study. J Clin Oncol. 2009;27:5175-81.3. 中国临床肿瘤学会(CSCO). CSCO儿童及青少年白血病诊疗指南(2023)[M]. 北京: 人民卫生出版社.4. Roberts KG, Li Y, Payne-Turner D, et al. Targetable kinase-activating lesions in ph-like acute lymphoblastic leukemia. N Engl J Med. 2014;371:1005-15.5. Mian AA, Schull M, Zhao Z, et al. The gatekeeper mutation t315i confers resistance against small molecules by increasing or restoring the abl-kinase activity accompanied by aberrant transphosphorylation of endogenous bcr, even in loss-of-function mutants of bcr/abl. Leukemia. 2009;23:1614-21.6. 石大雨秦, 赖悦云, 等. BCR-ABL激酶区突变在酪氨酸激酶抑制剂耐药慢性髓性白血病患者中的分布及其影响因素 [J] . 中华血液学杂志, 2020, 41(6) : 469-476.7. Ren X, Pan X, Zhang Z, et al. Identification of gzd824 as an orally bioavailable inhibitor that targets phosphorylated and nonphosphorylated breakpoint cluster region-abelson (bcr-abl) kinase and overcomes clinically acquired mutation-induced resistance against imatinib. J Med Chem. 2013;56:879-94.8. Senapati J, Sasaki K, Issa GC, et al. Management of chronic myeloid leukemia in 2023 - common ground and common sense. Blood Cancer J. 2023;13:58.9. 中国临床肿瘤学会(CSCO). CSCO儿童及青少年白血病诊疗指南(2025)[M]. 北京: 人民卫生出版社.10. Li X, Zhang J, Liu F, et al. Olverembatinib treatment in pediatric patients with relapsed philadelphia-chromosome-positive acute lymphoblastic leukemia. Clin Lymphoma Myeloma Leuk. 2023;23:660-6.11. 郑方圆丁明明陆爱东贾月萍曾慧敏张乐萍. 奥雷巴替尼治疗复发费城染色体阳性急性淋巴细胞白血病患儿8例病例系列报告 [J].中国循证儿科杂志, 20(1): 22-26.12. Zhang J, Wang J, Guo H, et al. Safety and efficacy of olverembatinib (hqp1351) combined with lisaftoclax (apg-2575) in children and adolescents with relapsed/refractory philadelphia chromosome-positive acute lymphoblastic leukemia (r/r ph+ all): First report from a phase 1 study. Blood. 2024;144:1443-.本文旨在为医疗卫生专业人士传递更多医学信息，不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，信达不推荐任何未获批的药品/适应症使用。

CSCO会议临床结果突破性疗法临床1期

100 项与中国医学科学院血液病医院相关的药物交易

登录后查看更多信息

100 项与中国医学科学院血液病医院相关的转化医学

登录后查看更多信息

组织架构

使用我们的机构树数据加速您的研究。

或

查看完整样例数据

管线布局

2025年05月28日管线快照

管线布局中药物为当前组织机构及其子机构作为药物机构进行统计，早期临床1期并入临床1期，临床1/2期并入临床2期，临床2/3期并入临床3期

药物发现

临床1期

临床2期

其他

登录后查看更多信息

当前项目

药物(靶点)	适应症	全球最高研发状态

Anti-GPRC5D CAR-T Cells(Institute of Hematology & Blood Diseases Hospital) ( GPRC5D )	难治性多发性骨髓瘤更多	临床2期
Humanized CD25 Monoclonal Antibody(Institute of Hematology & Blood Diseases Hospital) ( IL2RA )	急性移植物抗宿主病更多	临床2期
Anti-BCMA CAR-T(Institute of Hematology & Blood Diseases Hospital) ( BCMA )	残留肿瘤更多	临床2期
Anti-CD19 CAR T-cell therapy (Institute of Hematology and Blood Diseases Hospital of the Chinese Academy of Medical Sciences ) ( CD19 )	成人急性淋巴细胞白血病更多	临床2期
anti-HIV CAR-T Cell (Tsinghua University) ( Viral proteins )	获得性免疫缺陷综合征更多	临床1期