An Interventional, Prospective Open-Label Study of Immunosuppressive Therapies to Mitigate Immune-Mediated Loss of Therapeutic Response to Asfotase Alfa (STRENSIQ®) for Hypophosphatasia (RESTORE)

The primary objective of this study is to evaluate the effect of immunosuppressive therapy (IST) in participants treated with asfotase alfa who demonstrate immune-mediated loss of effectiveness (LoE).

开始日期2026-07-29

申办/合作机构

Alexion Pharmaceuticals, Inc.

NCT06348147

/ Suspended临床2期

An Attenuated Schedule Dara-RVd Induction for Patients With Newly Diagnosed Multiple Myeloma Who Are Eligible for Autologous Stem Cell Transplantation

This Phase II hybrid decentralized trial will examine the effect of daratumumab-based quadruplet induction therapy administered at an attenuated schedule in subjects with newly diagnosed multiple myeloma (NDMM) who are eligible for standard-of-care autologous stem cell transplantation (ASCT). Daratumumab, lenalidomide, bortezomib, and dexamethasone (Dara-RVd) have recently become a standard induction regimen for patients with NDMM who are eligible for ASCT in the United States. As implemented in clinical trials, Dara-RVd involves twice weekly bortezomib administration, which is inconvenient for patients and may result in increased rates of limiting toxicity, such as peripheral neuropathy. Adoption of alternate schedules involving once-weekly bortezomib is common in real-world practice, however a paucity of prospective data supporting this practice exists.
This study examines the efficacy of an attenuated Dara-RVd schedule involving once-weekly bortezomib dosing.

开始日期2026-07-01

申办/合作机构

Lineberger Comprehensive Cancer Center

NCT07072585

/ Not yet recruiting临床2/3期IIT

A Phase 2/3 Randomized Trial Investigating Daratumumab on a Modified Augmented BFM (aBFM) Backbone in Newly Diagnosed T-Lymphoblastic Leukemia (T-ALL) and T-Lymphoblastic Lymphoma (T-LL)

This phase II/III trial tests the addition of daratumumab to chemotherapy for treating patients with newly-diagnosed T-ALL and T-LL. Daratumumab is in a class of medications called monoclonal antibodies. It binds to a protein called CD38, which is found on some types of immune cells and cancer cells. Daratumumab may block CD38 and help the immune system kill cancer cells. Chemotherapy drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy with daratumumab may kill more cancer cells.

开始日期2026-06-28

申办/合作机构

The Children's Oncology Group Foundation, Inc.

100 项与硼替佐米相关的临床结果

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100 项与硼替佐米相关的转化医学

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100 项与硼替佐米相关的专利（医药）

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12,094

项与硼替佐米相关的文献（医药）

2026-12-31·ANNALS OF MEDICINE

Frequency-adjusted daratumumab-based regimen versus bortezomib/dexamethasone in newly diagnosed AL amyloidosis: a matched-cohort study

Article

作者: Li, Wenjing ; Zheng, Wanting ; Zhou, Meilan ; Liu, Baojian ; Zhao, Jin ; Xing, Yan ; Sun, Shiren

BACKGROUND:

The optimal dosing schedule for daratumumab (Dara) in newly diagnosed systemic light-chain (AL) amyloidosis requires refinement. This real-world study compared the efficacy and safety of a frequency-adjusted, cyclophosphamide-free Dara-based regimen with bortezomib/dexamethasone (BD).

METHODS:

We included newly diagnosed AL amyloidosis patients treated between January 2018 and December 2024, with follow-up data censored in August 2025. Using 1:1 propensity score matching based on age, cardiac stage, dFLC, and organ function, we compared hematologic/organ responses and survival. Survival was analyzed with Kaplan-Meier and log-rank tests. The Dara-based group received a cyclophosphamide-free regimen with an adjusted schedule (biweekly in cycle 1, then monthly) and a response-guided treatment duration.

RESULTS:

A total of 105 patients were included. After propensity score matching, 60 patients (30 per group) were selected for comparative analysis. The Dara-based group achieved significantly higher hematologic complete response (CR) rates at 6 months (57% vs. 27%, p = 0.018) and 12 months (63% vs. 27%, p = 0.002), with a markedly shorter median time to CR (61 vs. 120 days, p = 0.010). Organ responses were also superior: cardiac response 52% vs. 24% (p = 0.037) and renal response 56% vs. 27% (p = 0.037). No significant survival difference was observed during follow-up, and the safety profile was comparable between groups.

CONCLUSION:

A frequency-adjusted Dara-based regimen induces significantly faster and deeper hematologic and organ responses compared to BD in newly diagnosed AL amyloidosis which offers a promising personalized approach to reduce treatment burden and adverse events while maintaining high efficacy, supporting its integration into clinical practice for a broader patient population.

2026-12-31·JOURNAL OF MEDICAL ECONOMICS

Indirect treatment comparison of DVRd plus DR maintenance (PERSEUS study) versus DVTd or VTd with or without lenalidomide maintenance in transplant-eligible patients with previously untreated multiple myeloma

Article

作者: He, Jianming ; Nair, Sandhya ; Einsele, Hermann ; Facon, Thierry ; Dimopoulos, Meletios A. ; Caillot, Denis ; Sonneveld, Pieter ; Zweegman, Sonja ; Ammann, Eric ; Nobrega, Marjorie ; Broijl, Annemiek ; Spencer, Andrew ; Perrot, Aurore ; Schjesvold, Fredrik ; Gay, Francesca ; Hajek, Roman ; Boccadoro, Mario ; Rodriguez-Otero, Paula ; Hulin, Cyrille ; Sitthi-Amorn, Anna ; Rowe, Melissa ; Leleu, Xavier ; Mina, Roberto

AIMS:

To compare the effectiveness of induction and consolidation with daratumumab, bortezomib, lenalidomide, and dexamethasone (DVRd) plus maintenance therapy with daratumumab and lenalidomide (DR) with 2 treatment regimens that are widely used for transplant-eligible newly diagnosed multiple myeloma (TE NDMM): bortezomib, thalidomide, and dexamethasone (VTd) or daratumumab-VTd (DVTd) followed by observation (Obs) or lenalidomide maintenance.

MATERIALS AND METHODS:

Individual patient-level data from the PERSEUS (NCT03710603) and CASSIOPEIA (NCT02541383) trials were used to compare DVRd + DR with VTd + Obs and with DVTd + Obs. Inverse probability of treatment weighting was used to adjust for differences in baseline patient characteristics between the two trials; inverse probability of censoring weighting was used to adjust for the second randomization of CASSIOPEIA. Data from the CASSIOPEIA and Myeloma XI (EudraCT 2009-010956-93) trials were combined to model outcomes associated with lenalidomide (R) maintenance following induction with DVTd or VTd.

RESULTS:

DVRd + DR showed superior progression-free survival compared with DVTd + Obs (hazard ratio, 0.39 [95% CI = 0.26-0.59]), VTd + Obs (0.17 [95% CI = 0.12-0.25]), DVTd + R (0.62 [95% CI = 0.41-0.92]), and VTd + R (0.29 [95% CI = 0.18-0.43]). Sensitivity analyses showed results were consistent with the base case.

LIMITATIONS:

The indirect treatment comparison was unanchored due to a lack of common comparators and relied on external data from the Myeloma XI trial to model outcomes associated with DVTd or VTd followed by R maintenance. Despite best efforts to identify and adjust for important treatment effect modifiers, there is a potential for residual confounding.

CONCLUSIONS:

Findings from this study suggest that DVRd followed by DR maintenance offers superior survival outcomes compared with current standards of care in TE patients with NDMM.

2026-12-01·MOLECULAR BIOLOGY REPORTS

Inhibition of interleukin-1 receptor-associated kinase (IRAK)-4 provides partial rescue of interleukin-1 beta induced functional and gene expression changes in equine tenocytes

Article

作者: Guest, Deborah Jane ; Flood, Caroline ; Beaumont, Ross Eric

Abstract:

Background:

Interleukin 1 beta (IL-1β) is upregulated following a tendon injury and in vitro studies have shown that it leads to numerous negative effects on tendon cell function and gene expression. IL-1β activates nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and we hypothesised that inhibiting NF-κB activation would mediate the negative effects of IL-1β on equine tendon cells in 3-dimensional (3D) cultures.

Methods and results:

Here, we tested three inhibitors of NF-κB signalling (Bortezomib, BAY11-7082 and Wedelolactone) along withTJ-M2010-5, an inhibitor of MyD88, which is a critical adaptor protein for mediating IL-1β signalling. None of these inhibitors were able to rescue gel contraction by equine tenocytes exposed to IL-1β in 3D culture. However, the daily application of the interleukin-1 receptor-associated kinase (IRAK)−4 inhibitor PF-06650833 resulted in a partial rescue of collagen contraction and interleukin-6 (IL-6) production by equine tenocytes in 3D culture. Global gene expression using RNA sequencing also revealed a partial rescue, although this was not as complete as that achieved using interleukin-1 receptor antagonist protein (IL1Ra), with many inflammatory pathways remaining upregulated. ENPP2 expression was significantly increased by IL-1β and rescued by both IL1Ra and PF-06650833 suggesting ENPP2 may be involved in collagen contraction. However, direct ENPP2 inhibition does not rescue IL-1β mediated inhibition of contraction and ENPP2 inhibition alone reduces collagen contraction.

Conclusions:

Together, this data demonstrates that IL-1β has a broad mechanism of action on tendon cells which cannot be fully mediated by targeting specific parts of the signalling pathway.

1,452

项与硼替佐米相关的新闻（医药）

2026-03-26

·临床肾脏病杂志

文章选读|冷球蛋白血症肾病的研究进展

冷球蛋白血症肾病的研究进展符之莲韩辉（海南医科大学附属海南医院/海南省人民医院肾内科，海口 570311） DOI：10.3969/j.issn.1671-2390.2026.02.013 摘要冷球蛋白血症肾病（cryoglobulinemic nephropathy，CN）是由于冷球蛋白沉积引发的肾脏损害。冷球蛋白是一类在温度低于37 ℃时出现沉淀、复温后又可重新溶解的异常循环免疫球蛋白，当血液中存在循环冷球蛋白时称为冷球蛋白血症（cryoglobulinemia，CG）。根据冷球蛋白的组成可分为3型，其中Ⅱ型和Ⅲ型CG统称混合型冷球蛋白血症（mixed cryoglobulinemia，MC）。约1/3的MC患者会出现肾脏受累，Ⅰ型CG也可累及肾脏，且肾脏受累通常提示患者预后不良。本文就CN的病因、发病机制、临床表现、诊断以及治疗的最新进展进行综述。关键词冷球蛋白血症肾病；临床表现；诊断；治疗冷球蛋白血症（cryoglobulinemia，CG）是一种全球罕见的疾病，其患病率<5/10万，男女比例为1∶3，发病年龄通常在42~52岁［1］。该病具有明显的地理差异，南欧的发病率高于北欧和北美，这与丙型肝炎病毒（hepatitis C virus，HCV）感染的流行率相关［2］。1974年Brouet等根据冷球蛋白的组成将CG分为3型，Ⅰ型由单克隆免疫球蛋白（immunoglobulin，Ig）组成，通常为IgG或IgM，少数为IgA或游离轻链，占10%~15%［3］；Ⅱ型由具有类风湿因子（rheumatoid factor，RF）活性的单克隆IgM和多克隆IgG组成；Ⅲ型由具有RF活性的多克隆IgM和多克隆IgG组成。其中Ⅱ型和Ⅲ型均可形成免疫复合物，统称为混合型冷球蛋白血症（mixed cryoglobulinemia，MC），二者分别占50%~60%和25%~30%［3］。由于CG发病率低、中国开展冷球蛋白检测的中心有限，且检测对样本采集和实验室技术要求较高，加之临床医生对该病认识不足，故患者肾脏受累时，临床医生往往未能及时考虑CG的可能性［4］。本文就冷球蛋白血症肾病（cryoglobulinemic nephropathy，CN）的临床表现、诊断及治疗的最新研究进展作综述。一、发展历史 1933年，Wintrobe于1例多发性骨髓瘤患者体内发现一种循环Ig能在体外冷却到4 °C时出现沉淀，但重新加热后可逆溶解。1947年，Lerner和Watson开始将这些蛋白质命名为冷球蛋白。1966年，Meltzer首次描述29例CG患者的典型临床特征，包括关节痛、紫癜和虚弱。1974年，Brouet等根据冷球蛋白组成分为3型，该分型（Brouet分型）是目前最广泛用于区分CG的分型方法。有研究指出，Ⅲ型CG是Ⅱ型从多克隆向寡单克隆B淋巴细胞群转化的过渡类型［5］。1989年人类首次发现HCV，并于20世纪90年代初发现CG与慢性HCV感染有关［6］，2011年直接抗病毒药物（direct-acting antivirals，DAA）开始应用于临床治疗后，与HCV相关CG的发病率持续下降［7］。二、病因（一）原发性病因 CG病因分为原发性和继发性，当在没有明确基础疾病的情况下发现MC时，该综合征称为原发性MC。超过90%的CG患者有已知的潜在病因，近10%的MC患者被认为是特发性或原发性，尤其在HCV阴性患者中，这一比例可上升至25%［8］。其发生机制可能与遗传和（或）环境因素有关。（二）继发性病因 1. HCV感染根据世界卫生组织最新数据，全球HCV感染人数约5000万，每年新增感染约100万例。慢性HCV感染曾是MC的主要病因，占80%~90%［7］。HCV可诱发多种B淋巴细胞的淋巴组织增生性疾病，包括高丙种球蛋白血症、MC、边缘区淋巴瘤及B淋巴细胞非霍奇金淋巴瘤（B-cell non-hodgkin's lymphoma，B-NHL），其机制可能为淋巴细胞与肝细胞表面均有CD81跨膜受体，HCV病毒包膜蛋白E2与该受体结合并导致淋巴细胞稳态的多种变化，这种级联反应可引发CG、冷球蛋白血症血管炎（cryoglobulinemic vasculitis，CV），并最终导致B-NHL，这些均为HCV的肝外表现［9］。然而，自2011年DAA广泛应用后，慢性HCV感染已不再是MC的主要病因［7］。 2. 非HCV病毒感染 CG常与血液系统疾病、自身免疫性疾病及乙肝病毒（hepatitis B virus，HBV）、人类免疫缺陷病毒（human immunodeficiency virus，HIV）感染等相关。Ⅰ型CG仅见于克隆性增殖性血液病，主要发生于B淋巴细胞恶性肿瘤，如意义未明的单克隆丙种球蛋白病（约40%）、华氏巨球蛋白血症（waldenström macroglobulinemia，WM）、多发性骨髓瘤（multiple myeloma，MM）及慢性淋巴细胞白血病［10］。目前，MC的主要病因已从HCV感染转变为系统性自身免疫性疾病（如系统性红斑狼疮和干燥综合征）及血液系统恶性肿瘤［9］。国外研究显示，HCV相关CG的患病率是HBV的2~4倍［3］。因中国HBV感染更为普遍，多项研究表明与西方国家相比，乙型肝炎是中国CG的常见病因［11］。其他罕见病因包括细菌、真菌、寄生虫感染、人疱疹病毒4型、巨细胞病毒感染，以及腺癌、鼻咽癌和食道癌等恶性肿瘤［12］。三、发病机制冷球蛋白是由B淋巴细胞克隆扩增产生的，通常与淋巴增生性疾病、慢性感染或自身免疫性疾病引起的持续免疫刺激相关。Ⅰ型和Ⅱ型CG由单克隆B淋巴细胞扩增引起，而Ⅲ型则为多克隆B淋巴细胞扩增引起［8］。冷球蛋白主要影响中小型血管，导致内皮损伤和终末器官损害，引发一系列临床症状。在不同类型的CG中，2种主要机制起不同程度的作用［13］：Ⅰ型主要表现为凝血障碍，由低温诱导的冷球蛋白聚集引起微循环机械性阻塞，如高黏滞和血栓形成，通常较少涉及补体；而MC则主要由补体介导的免疫复合物沉积引发自身免疫性小血管炎。Strait等［14］通过建立CG性肾病小鼠模型，证实免疫复合物在肾小球毛细血管中的沉积是主要致病机制，而非补体依赖性或结晶片段（fragment crystallizable，Fc）受体依赖性肾毒性机制。沉积在肾实质中的免疫复合物会招募巨噬细胞，但巨噬细胞因单核细胞溶酶体的改变，导致其通过Ig的Fc-γ受体清除免疫复合物的能力下降。同时，免疫复合物会激活并消耗补体，导致补体C3功能下降，Ⅰ型补体受体下调，进而减少免疫复合物向肝脏和脾脏的巨噬细胞转运和清除。因此，MC肾脏受累的发病机制与免疫复合物形成和巨噬细胞清除功能缺陷之间的失衡密切相关［15］。近年来研究发现，中性粒细胞外陷阱（neutrophil extracellular traps，NET）在免疫介导的CN中起重要作用。NET由活化的中性粒细胞释放，含有中性粒细胞颗粒、染色质、组蛋白和自身抗原，可维持炎症反应，其可促进体液免疫反应和免疫复合物沉积，从而推动以NET增加为特征的自身免疫性肾病的进展。使用CIT-013等药物抑制NET形成或促进其清除，有助于阐明NET在自身免疫中的作用［16］。四、临床表现 CG常无明显症状，可能偶然通过实验室检查发现，当出现临床症状时称为CV。约30%的CG患者会累及肾脏［10］，其中1/3为MC，少数为Ⅰ型CG［13］。研究表明，冷球蛋白水平每增加100 mg/L，肾脏受累风险上升10%［17］。肾脏受累通常预后较差，且HBV相关CG的肾脏结局较HCV相关者更差［11］。马逸辰等［4］分析202例CG患者，发现43.1%首诊时表现为肾脏损害，其中Ⅱ型和Ⅲ型患者的肾脏损害发生率（分别为56.9%和52.4%）显著高于Ⅰ型患者（17.7%，P均<0.05）。CN通常呈惰性病程，进展缓慢，常见表现为膜增生性肾小球肾炎（membrano-proliferative glomerulonephritis，MPGN），但急性肾功能衰竭和肾炎综合征也可作为首发表现［9］。临床表现包括镜下血尿（97.4%）、高血压（85.3%）、蛋白尿（84.8%，其中49.4%为肾病程度蛋白尿）及不同程度的肾功能不全（82.3%），严重感染是其主要死亡原因［18］。有研究指出，蛋白尿和镜下血尿是CN主要临床表现［12］。 CG可累及肾脏以外的多个器官，肾外症状通常早于肾脏症状数年出现，但约30%的患者可能同时出现［19］。复发性可触及紫癜是最常见的表现（90%），其组织学特征为白细胞破碎性血管炎。其他常见症状包括双侧对称的手及膝关节非游走性疼痛（50%~75%）和周围神经病变（20%）［20］。此外，CG也可能罕见地累及胃肠道、中枢神经系统、心脏和肺部，发生率均<5%，表现为腹痛、脑部局灶性缺损或神经认知障碍、心肌梗死及心力衰竭、闭塞性细支气管炎、机化性肺炎和肺泡出血综合征［12］。患者出现疲劳和间歇性发热时，通常提示疾病复发。五、诊断目前国际上尚无标准化的CG的诊断标准，其诊断主要依靠血清冷球蛋白检测及典型的临床表现。一项大型研究发现有9% 的CG患者有假阴性检测［21］，为避免出现假阴性结果及过早的低温沉淀，血液样本采集、运送及离心均在37 ℃下进行，离心后置于Wintrobe管中并4 °C冷藏7 d，每日观察沉淀情况，7 d后仍无沉淀出现报告为阴性，期间若出现沉淀物，将其重新复温至37 ℃，如沉淀重新溶解，则冷球蛋白定性为阳性。冷球蛋白定性检测为阳性的血清待进行冷球蛋白纯化后可测定冷比容、免疫电泳或免疫固定以量化冷球蛋白水平及鉴定冷球蛋白的类型［22］。但不同类型冷球蛋白沉淀的时间有所不同，Ⅰ型CG在24 h内表现为沉淀，有3~5 d的窗口期，而混合型（Ⅱ/Ⅲ型）沉淀多出现在冷藏后5~7 d［23］。由于传统免疫电泳敏感度低具有较高的假阴性率，免疫固定电泳时大分子IgM会堵塞凝胶孔易影响结果，免疫印迹法操作复杂难以应用临床，秦绪珍等［24］推荐采用改良毛细管电泳免疫技术，该方法具有可控温、样本量小、液相分离等优势，可显著提高检测的灵敏度和准确性。对于血清冷球蛋白阴性但高度怀疑CV的患者，建议连续复查冷球蛋白检测，并结合其他辅助检查以明确诊断，包括病毒血清学（如HCV、HBV、HIV）、自身免疫系统抗体（如抗核抗体、抗dsDNA、抗干燥综合征A抗体、抗干燥综合征B抗体、抗中性粒细胞胞浆抗体）、RF及补体C4水平、急性期反应物、Ig水平（IgG、IgM、IgA）、影像学检查（X线、B型超声、肌电图）等，必要时完善病变部位组织活检（如皮肤、肾脏或周围神经）［25］。有文献报道，CN检测冷球蛋白时存在较高假阴性率，高度怀疑CN时，肾活检可有助于协助诊断［26］。CN主要累及肾小球，而较少累及肾小管，其病理类型以MPGN最为常见，其他类型包括局灶性肾小球肾炎和膜性肾小球肾病［27］。在光学显微镜下，冷球蛋白相关肾炎通常表现为MPGN，伴有大量单核细胞浸润及（假性）血栓形成；电镜下显示系膜区和内皮下微管状或晶体状沉积物，并伴有单核细胞/巨噬细胞浸润；免疫荧光染色特征因冷球蛋白类型而异［28］。杨佳茹等［29］提出，CG肾损害的诊断常见于三种情况：（1）临床化验显示冷球蛋白阳性，电镜下可见出现特殊结晶状物质。（2）临床检出冷球蛋白，电镜检查未见冷球蛋白沉积，原因是冷球蛋白未在肾小球内弥漫沉积。（3）临床未检查出冷球蛋白，但电镜下发现冷球蛋白沉积物，可确诊为CG肾损害，此时需怀疑是临床取样不当导致冷球蛋白检测阴性。六、治疗 CG的治疗需根据其类型、潜在病因及器官受累程度制定个体化方案，其中紫癜、雷诺现象、血液系统疾病及冷沉淀物水平可作为评估疾病严重程度，并帮助制定临床决策和护理方案［30］。目前的主要治疗策略包括病因治疗、常规免疫抑制剂和生物制剂治疗，治疗目标是阻断感染或自身免疫性病因对B淋巴细胞的刺激，通过免疫抑制或靶向治疗抑制B淋巴细胞的增殖和分化，清除血清中的冷球蛋白并改善症状。（一）一般治疗早期识别CG临床症状并及时治疗，可有效预防器官损伤及疾病进展，因此健康教育是治疗的重要组成部分。同时，保持健康生活方式，如减少饮酒、戒烟及遵循低抗原饮食，有助于降低CV发作风险。由于CG患者免疫功能较弱，感染风险较高，建议接种流感、肺炎球菌、水痘、带状疱疹等疫苗［23］。尽管疫苗接种可能诱导自身免疫疾病［23］，但对CV患者而言，其益处远大于风险。对于Ⅰ型CG患者，应避免寒冷刺激与外伤、加强足部和腿部护理以预防伤口并发症。对于仅有紫癜的患者可通过穿戴压力袜有效改善症状。（二）分型治疗 1. Ⅰ型CG 对于无症状的CG患者，建议定期随访观察。有症状的Ⅰ型CG患者通常与血液系统疾病相关，治疗策略主要基于针对潜在血液病的特定药物。若缺乏治疗血液学疾病的明确指征，则需根据Ig类型制定治疗方案［13］。对于IgM型患者，利妥昔单抗（rituximab，RTX）、烷化剂及Bruton酪氨酸激酶抑制剂常作为首选治疗。而IgG介导型患者则可采用硼替佐米、抗CD38药物（如艾沙妥昔单抗、达雷妥尤单抗）或免疫调节剂（如来那度胺、沙利度胺）。目前，一项针对IgG Ⅰ型CG的抗CD38治疗临床试验（注册号：NCT05114109）正在进行中，但尚无针对IgM的Ⅰ型CG试验数据［31］。此外，Ⅰ型CG可能引发体温依赖性血清高黏滞综合征，常见于WM和MM患者，需通过血浆置换快速降低血液黏度以缓解症状［32］。 2. MC （1）HCV相关性MC：对于无症状或轻度症状的CG患者，推荐单用泛基因型DAA治疗［33］。研究表明，8或12周的固定剂量泛基因型DAA方案具有较高的持续病毒学反应率（SVR>90%）、良好的安全性和耐受性，并可减少免疫抑制剂的使用［34］。对于中重度患者，建议在RTX治疗的同时或之后联合DAA，必要时可短期加用低至中等剂量糖皮质激素，以缓解血管炎发作和关节痛，但糖皮质激素不宜作为维持治疗［33］；RTX通过改善血管炎、降低RF水平、使补体C4水平正常化以及清除骨髓和外周血中的B淋巴细胞克隆，已被证实对CG具有显著疗效［33］。然而，RTX治疗可能引发高致死率的血管炎（>50%），尤其在CN患者中更为常见（P=0.0008），其肾脏病恶化机制可能与免疫复合物沉积引起的毛细血管内增生及CG和RTX导致的肾小球阻塞有关，为减少不良反应，建议在RTX治疗时联合使用皮质类固醇和抗组胺药［35］。对结果进展迅速或危及生命的患者，如急性肾功能衰竭、肠缺血、肺出血和（或）中枢神经系统受累［36］，给予糖皮质激素脉冲治疗、血浆置换、环磷酰胺或RTX，待病情稳定时再加用DAA。（2）非HCV相关性MC：病毒和化脓性细菌感染是非HCV感染性混合CV的主要原因，使用皮质类固醇治疗可能会产生不利影响，因此免疫抑制剂应仅在难治性或危及生命的血管炎患者中作为二线治疗方案［37］。目前，HBV相关CV（HBV-CV）尚无专门的治疗指南，其管理可参考HCV相关CV的治疗策略［38］。对于轻至中度HBV-CV患者，核苷酸类似物抗病毒治疗是首选。对于无反应、复发或重症患者（如皮肤溃疡、严重周围神经病变或肾脏疾病），可在抗病毒治疗基础上联合RTX或血浆置换。然而，目前针对非感染性MC的循证治疗建议较为有限。其通常与B淋巴细胞活性过高的自身免疫性疾病（如系统性红斑狼疮或干燥综合征）相关，治疗应基于对基础疾病的控制。对于轻中度患者，治疗选择包括休息、避免低温、使用非甾体抗炎药及秋水仙碱。若出现严重或危及生命的症状，则需采用皮质醇、免疫抑制剂、血浆置换及RTX的联合治疗方案［39］。值得注意的是，Lesniak等［40］首次报道COPA基因与非感染性CV相关，这一发现提示CG的发病机制可能与遗传因素有关，针对基因治疗或将成为未来新的治疗策略。（三） CN治疗 CN临床表现可为蛋白尿和高血压，应根据需要使用控制血压和减少蛋白尿药物进行肾脏保护治疗，如肾素-血管紧张素系统抑制剂、血管扩张剂、利尿剂及降脂药，若进展至终末期肾病通常需要透析或肾移植。大量蛋白尿患者可能发生容量负荷，应定期对患者进行称重并进行体液平衡评估，必要时限制液体和盐摄入，并合理使用利尿剂［41］。对于白蛋白<30 g/L且24 h尿蛋白量>3 g（尿白蛋白/肌酐比>300 mg/g）的患者，血栓风险较高，建议预防性使用依诺肝素或阿哌沙班抗凝治疗［41］。HCV相关肾小球病的治疗包括抗病毒、免疫抑制剂、大剂量糖皮质激素及血浆置换。根据改善全球肾脏病预后组织2022指南，HCV相关CV患者建议DAA联合免疫抑制剂，必要时增加血浆置换。对于抗病毒治疗无反应或GFR进行性下降的患者，RTX应作为首选免疫抑制治疗。低剂量（每周250 mg/m²，持续2周）与高剂量（每周375 mg/m²，持续4周或间隔2周1 g）的RTX在治疗某些中重度CV中疗效相当。然而，对于快速进展性肾小球肾炎、肺泡出血、肠血管炎或中枢神经系统血管炎等危及生命的病情，建议优先使用高剂量RTX方案。值得注意的是，RTX治疗可能激活HBV，因此在HBV携带者中应谨慎使用，并在治疗期间定期监测乙肝表面抗原和HBV DNA［42］。单采术（therapeutic apheresis，TA）在肾脏受累患者中显示出78%的高反应率［43］。然而目前，TA治疗尚无统一标准方案，包括治疗方式、频率和疗程数，但通常在强化治疗期间需进行2个周期的6次疗程，频率为每周2~3次，之后可能转为每周1次［43］。TA启动时机至关重要，应在RTX输注前或输注后7d内进行，因TA有助于清除RTX，尤其是在给药后3~7 d内［43］。但TA治疗无法根治基础疾病，且可能引发冷球蛋白反弹，需联合环磷酰胺（最长6周）预防反弹［8］。对于非感染性混合型冷球蛋白肾小球肾炎，推荐类固醇联合环磷酰胺或RTX作为一线治疗，其疗效优于单用类固醇，且更有效预防复发。（四）新兴治疗 1. 卡非佐米卡非佐米是一种新型蛋白酶体抑制剂，通过不可逆地选择性结合β5亚基抑制蛋白酶体活性，适用于复发性/难治性MM。Yasuda等［44］报道了1例对硼替佐米和达雷妥尤单抗治疗无效的CV患者，改用卡非佐米、环磷酰胺和地塞米松联合治疗后，冷球蛋白迅速消失且症状显著改善。这一案例表明，卡非佐米联合疗法可能为难治性CG患者提供了一种有前景的治疗选择。 2. 新型RTX和RTX类似物新型抗CD20单克隆抗体的开发旨在克服RTX的免疫原性并增强B淋巴细胞耗竭。例如，Obinutuzumab已被证实对RTX耐药的肾小球受累MC及RTX过敏患者有效［25］。此外，RTX生物仿制药CT-P10已在欧洲获批用于RTX的所有适应证。一项意大利研究分析对比了51例接受CT-P10治疗的CV患者与75例接受RTX原药治疗的患者，结果显示两组在疗效和免疫介导的不良事件方面差异无统计学意义，但CT-P10的成本/效率比更高［45］。因其成本/效率比，CT-P10有望取代RTX，甚至成为难治性CV的治疗方案。 3. 贝利尤单抗（belimumab，BMB） B淋巴细胞活化因子（B cell activating factor，BAFF）属于肿瘤坏死因子超家族，通过促进B淋巴细胞增殖和分化，导致Ig合成增加。BAFF水平升高与CV的发病机制密切相关［46］。因此针对BAFF轴和B淋巴细胞的治疗可能为CV患者，尤其是RTX难治性患者，提供一种新的有效策略。研究表明，RTX难治性患者通常具有以下特征：女性为主、年龄>50岁、伴有单克隆IgM κ成分的Ⅱ型CG、原发性干燥综合征及CG性MPGN［47］。一项研究显示，4例RTX难治性或复发的CV患者在接受BMB联合RTX治疗后病情显著改善［48］。然而，值得注意的是，接受抗CD20联合BMB治疗的患者中，57%出现了严重感染［49］。 4. 低剂量白细胞介素（interleukin，IL）2和嵌合抗原受体T淋巴细胞（chimeric antigen receptor T-cell，CAR-T）免疫疗法低剂量IL-2有望成为难治性CG的替代治疗方案［13］。一项1~2a期前瞻性开放标签研究表明，IL-2可恢复调节性T淋巴细胞与效应T淋巴细胞之间的平衡，并显著改善临床症状。系统性红斑狼疮是MC的主要病因之一，一项研究显示，5例对多种免疫抑制剂治疗无效的系统性红斑狼疮患者通过使用靶向CD19的CART免疫疗法，取得了良好的耐受性和显著疗效［50］。尽管CART免疫疗法有望成为治疗难治性和CV的未来选择，但目前尚无相关病例数据支持。七、展望 CG的病因和临床表现具有高度异质性，自2014年引入DAA并广泛使用RTX以来，CV格局发生显著改变。然而，未来研究应重点关注原发性CV及非HCV相关CV，尤其是自身免疫性疾病相关CV。此外，还需开展前瞻性研究和临床试验进一步探索难治性或复发性CV的治疗策略及其预后因素。目前重要且尚未解决的问题是制定冷球蛋白检测方法的标准化，同时开发鉴定新的遗传标志物和替代生物标志物对于CV的早期诊断至关重要，例如，CV患者APOA1和PCSK9水平的升高可为CV发病机制研究和生物标志物提供新的视角［51］，此外靶向APOA1和PCSK9的药物可能成为治疗CV的新疗法，但其潜在机制和研究现状仍需进一步探讨。继发于HCV的CG、CV和B-NHL为研究自身免疫性疾病和淋巴组织增生性疾病的发病机制提供重要的研究模型，特别是探讨从淋巴细胞依赖性激活到非依赖性激活的转变，以及恶性细胞转化过程中关键检查点的作用机制。此外，未来还需开展更多研究，阐明DAA是否可能对CV患者的B-NHL 发展产生积极影响。最后，应进一步评估疾病负担、复发及治疗对患者身心健康和日常生活的影响，这有助于全面评估患者生活质量及优化管理策略提供重要依据。利益冲突声明所有作者均声明没有利益冲突 1. 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Hepatitis B virus-infection related cryoglobulinemic vasculitis. Clinical manifestations and the effect of antiviral therapy: a review of the literature[J]. Front Oncol, 2023, 13: 1095780. DOI: 10.3389/fonc.2023.1095780. 39. Perez-Alamino R, Espinoza LR. Non-infectious cryoglobulinemia vasculitis (CryoVas): update on clinical and therapeutic approach[J]. Curr Rheumatol Rep, 2014, 16(5): 420. DOI: 10.1007/s11926-014-0420-0. 40. Leśniak K, Płoski R, Rydzanicz M, et al. Non-infectious mixed cryoglobulinemia as a new clinical presentation of mutation in the gene encoding coatomer subunit alpha: a case report of two adult sisters[J]. Front Immunol, 2024, 15: 1450048. DOI: 10.3389/fimmu.2024.1450048. 41. Pinney J, Roufosse C, Kousios A, et al. Diagnosis and management of monoclonal gammopathy of renal significance: a British Society for Haematology good practice paper[J]. Br J Haematol, 2025, 206(2): 447-463. DOI: 10.1111/bjh.19956. 42. Quartuccio L, Bortoluzzi A, Scirè CA, et al. Management of mixed cryoglobulinemia with rituximab: evidence and consensus-based recommendations from the Italian Study Group of Cryoglobulinemia (GISC)[J]. Clin Rheumatol, 2023, 42(2): 359-370. DOI: 10.1007/s10067-022-06391-w. 43. Miao J, Krisanapan P, Tangpanithandee S, et al. Efficacy of therapeutic apheresis for cryoglobulinemic vasculitis patients with renal involvement: a systematic review[J]. Blood Purif, 2024, 53(1): 1-9. DOI: 10.1159/000534102. 44. Yasuda Y, Maki H, Shimura A, et al. Successful treatment of type I cryoglobulinemia with a combination of carfilzomib, cyclophosphamide, and dexamethasone: a case report and literature review[J]. Int J Hematol, 2025, 121(3): 411-415. DOI: 10.1007/s12185-024-03911-z. 45. Vacchi C, Visentini M, Gragnani L, et al. Safety and effectiveness of biosimilar of Rituximab CT-P10 in the treatment of cryoglobulinemic vasculitis: the MARBLe study (Mixed cryoglobulinemiA Rituximab BiosimiLar)[J]. Intern Emerg Med, 2021, 16(1): 149-156. DOI: 10.1007/s11739-020-02386-0. 46. Moretti M, Ferro F, Baldini C, et al. Cryoglobulinemic vasculitis: a 2023 update[J]. Curr Opin Rheumatol, 2024, 36(1): 27-34. DOI: 10.1097/BOR.0000000000000989. 47. Rajendran N, Rameli PM, Awad H. Risk factors for relapse in non-infectious cryoglobulinemic vasculitis, including type I cryoglobulinemia: a systematic review[J]. Front Immunol, 2023, 14: 1215345. DOI: 10.3389/fimmu.2023.1215345. 48. Saadoun D, Ghembaza A, Riviere S, et al. Rituximab plus belimumab in non-infectious refractory cryoglobulinemia vasculitis: a pilot study[J]. J Autoimmun, 2021, 116: 102577. DOI: 10.1016/j.jaut.2020.102577. 49. Pouchelon C, Visentini M, Emmi G, et al. Management of nonviral mixed cryoglobulinemia vasculitis refractory to rituximab: Data from a European collaborative study and review of the literature[J]. Autoimmun Rev, 2022, 21(4): 103034. DOI: 10.1016/j.autrev.2022.103034. 50. Mackensen A, Müller F, Mougiakakos D, et al. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus[J]. Nat Med, 2022, 28(10): 2124-2132. DOI: 10.1038/s41591-022-02017-5. 51. Liu P, Wu JQ, Sun DD, et al. Proteomic profiling of cryoglobulinemia[J]. Front Immunol, 2022, 13: 855513. DOI: 10.3389/fimmu.2022.855513. Advances in cryoglobulinemic nephropathy Fu Zhi-lianHan Hui （Department of Nephrology， Hainan Medical University Hainan Hospital/Hainan General Hospital， Haikou 570311，China） Abstract: Cryoglobulinemic nephropathy （CN） is renal injury resulting from deposition of cryoglobulins. Cryoglobulins are abnormal circulating immunoglobulins that precipitate at temperatures below 37 °C and redissolve on warming； the presence of these proteins in the circulation is termed cryoglobulinemia （CG）. CG is classified into three types according to the immunoglobulin composition of the cryoglobulins. Types Ⅱ and Ⅲ are collectively known as mixed cryoglobulinemia （MC）. Renal involvement occurs in approximately one-third of patients with MC； type Ⅰ CG may also involve the kidney. The presence of renal disease typically portends a worse prognosis. This review summarizes recent progress in the etiology， pathogenesis， clinical presentation， diagnosis， and treatment of CN. Keywords: Cryoglobulinemic nephropathy；Clinical manifestations；Diagnosis；Treatment 引用本文：符之莲,韩辉.冷球蛋白血症肾病的研究进展[J].临床肾脏病杂志,2026,26(02):189-194. (Fu Zhi-lian,Han Hui.Advances in cryoglobulinemic nephropathy[J].Journal of Clinical Nephrology,2026,26(02):189-194.) 通讯作者：韩辉，Email：kendy66@126.com 文章编号：1671-2390（2026）02-0189-06 收稿日期：2025-03-31 出版日期：2026-02-28 网刊发布日期：2026-02-25

2026-03-25

·刀客特Q

从肿瘤新药指南看AI时代

你有没有想过，面对癌症，医生手中到底有多少种‘武器’可以选择？国家卫健委办公厅在2026年1月19日印发了2025年版本的《新型抗肿瘤药物临床应用指导原则（2025年版）》[1]，于是我们做了这件事：把这四年的指南放在一起做了个比对[1-4]，结果发现了一些非常有意思的现象。一、我们先看最基础的页数，这直接反映了指南的体量。从2022年的280页，到2023年的358页，再到2024年的439页，最终到2025年的605页。在三年时间里，指南的厚度增长了一倍还多，累计净增了325页，涨幅116%！尤其值得注意的是2025年，这一版比上一个年度就多了166页，增加了37.8%，增幅惊人。二、显而易见，增加的内容首先是方案数大幅增加。用药方案条目上从2022年的147条，跃升至2025年的261条。这意味着，可供医生参考的方案，在这三年里增加了近八成。三、相应的，是药物数量的飞跃。它从2022年的约103种，增长至2025年的约186种。三年增加了83种新药，临床医生手中的‘武器库’规模，在短短三年内累计增长80.6%。四、这一飞跃主要得益于多重动力的叠加： AI的发展加速了靶点发现与药物设计，同时，持续增加的研发投入、活跃的生物科技企业创新以及药政改革的深化，共同构成了强大的助推器，促进临床试验的数量与规模持续扩大，为新药研发提供了广阔平台。五、现在让我们更深入一步，把数据扒开再看看这张图统计了从2022至2025年，各部位推荐用药条目数。其中有三个点最引人注目：首先是2025年新增了大量用药方案；其次是呼吸系统和血液系统的推荐药物条目数极为丰富，且在这几年连年大幅增加；第三是自2023年起，《原则》开始纳入泛实体瘤推荐药物。另外值得注意的是，尽管绝大多数部位的药物种类数量呈现持续增长趋势，但个别系统在特定年份出现了净减少。如血液系统和骨与软组织肿瘤。而在这背后，其实是药物“有进有出”动态调整。一些药物是适用范围的变化，如斯鲁利单抗原本用于呼吸系统和消化系统，于2023年被纳入新增的“泛实体瘤“类中，随后又在2025年被移出此类。也有药物则因临床证据更新而被淘汰，如莫博赛替尼于2023年因III期EXCLAIM-2临床试验结果未达到主要研究终点退市。这种调整是目录更新的常态。六、更细致地来看，还可以发现以下变化：首先，药物覆盖的靶点逐渐铺开，更加全面。新增的药物中有药物可以针对新的靶点，如针对KRAS G12C突变的格索雷塞，针对HIF-2α的贝组替凡，同时一些罕见突变的适用范围也覆盖到了更多种类的疾病。其次，除开上述的罕见突变，针对一些常见突变或靶点的药物数量也大大增加。EGFR为靶点的药物进入“内卷时代”。在奥希替尼、阿美替尼、伏美替尼之后，新增了多个EGFR-TKI，如瑞齐替尼、利厄替尼等。众所周知，EGFR突变是肺癌中的常见突变类型，现在回头来看，这正好对应上了呼吸系统用药数大大增加。另一个显著扩容的是靶向PD-1/PD-L1的药物：从2022年的13种增加至2025年的22种，且大量药物在此期间增加了适用范围。同时国产PD-1/PD-L1全面崛起，涌现出如阿得贝利、普特利、赛帕利等药物，临床选择更加多元化。另外，还有一个非常的显著的变化，那就是ADC类药物和CAR-T类药物迅猛发展，大量新药涌现。从2022年的4种增长至2025年的11种不同ADC药物。尤其是2025年，ADC类药物新增了7条推荐。适应症范围从乳腺、消化、泌尿、血液扩展到呼吸、生殖，几乎覆盖所有主要实体瘤。而其中，明星药物德曲妥珠单抗在三年内从乳腺癌迅速扩展至消化、呼吸，成为跨癌种ADC典范。在这几年里，ADC的靶点从HER2到Trop-2、nectin-4、FRα，越来越丰富，为患者提供更多治疗选择。国产ADC在其中快速跟进，形成进口与国产并存的格局。CAR-T类药物则是在2023年实现了“零的突破”，从这一年开始《指导原则》中有了CAR-T药物，分别是伊基奥仑赛，阿基仑赛，瑞基奥仑赛，均用于治疗血液肿瘤。至2025年时，扩展到了5种，且同时包含国产和进口药物。标志着这种高度个性化、一次性治疗的创新疗法在中国获得正式临床地位。七、这一切对肿瘤患者而言，是根本性的重大利好：首先，最直接的体现是可选药物的急剧增加，这意味着每位患者找到有效治疗方案的概率大大提升。药物基数的扩大，使临床医生在制定个性化方案时，可调配的“武器”更多了。这种丰富性直接推动了第二个利好：药物联用方案的增多。因为当药物的基数增加时，理论上可形成的组合方案会呈几何级数增长，这为攻克耐药、提升疗效提供了更强大的“组合拳”。这些将直接影响到患者的治疗效果。正如我们所见到的，呼吸系统的可用药物数正在惊人地增长，而肺癌患者的生存期也得以大大延长。一份专家共识指出，第三代EGFR-TKI的陆续问世，让晚期EGFR突变肺癌患者的5年总生存率从之前的14.6%提升至28%，翻了近一番[5]。而这些新药、新组合要真正落地，离不开第三个直接利好：患者能参与的临床试验也大大增加了。对很多患者来说，这不仅是费用减免的机会，也是用到前沿疗法、获得新希望的重要途径。八、不过，这个变化也许会让医生的工作更难。因为问题不再是“有无药可用”，而是在同一适应症下，从多种机制、不同代际的药物中作出选择，这需要在疗效、毒副、耐药、费用乃至患者意愿之间反复权衡。在这个药物、技术爆炸般更新迭代的时代，医生们不仅要在医院里不断积攒临床经验，更要在幕后不断汲取新的知识。肿瘤的高度异质性更意味着没有“万能药”，现在医生可以借助基因检测这些手段，再加上不断更新的知识，从这么多选项里，帮患者找到更合适的方案。而在这一片信息的汪洋大海面前，AI将展现出无可比拟的优势，未来的医疗，必将进入AI时代。九、这就又关系到了最近非常火热的话题，AI能否取代医生？而在这一系列讨论后，我们的观点却非常反直觉：医生的角色反而更加不可替代。首先就是老生常谈的，医生的经验，是在真实的、复杂的世界中积攒的，是AI的数据库所不具有的，也不是当前的AI可用通过推理能准确判断的。从统计学的角度来说，医生积累的“先验”的质量，是治疗的关键。不过这也意味着将来对“好医生”的需求会更高，但要求也会更严苛。另外，也是很重要的一点，治疗不是数据运算。它关乎人。患者经济条件如何？他本人意愿是什么？是追求最长的生存期，还是生活质量？在事关生死的选择面前，怎样安抚病人的情绪？当患者意识到在命运的路口出现更多岔路供选择时，医生又该如何安抚患者选择的焦虑，给予患者勇敢走下去的信心？这些充满人情味的关怀和权衡，恰恰是AI的死角。AI无法像人类一样思考生老病死，生命的温度，最后还是需要人来提供。肿瘤治疗正从“缺药可用”进入“AI辅助，择优而用”的时代。对于这场变革，你怎么看待？欢迎在评论区聊聊你的观察。参考文献： [1]https://www.nhc.gov.cn/yzygj/c100068/202212/fd6148a5383246b1851dff937507bcb9.shtml [2]https://www.nhc.gov.cn/yzygj/c100068/202401/1d26e5c2254b4930ab6056f942ca9dbf.shtml [3]https://www.nhc.gov.cn/yzygj/c100068/202501/4b86cb63eb03400eb789f371316ecea1.shtml [4]https://www.nhc.gov.cn/yzygj/c100067/202601/460c2377aa294b55baacd339b8b19eb8.shtml [5] Chang GC, Kapoor A, Lee CK, et al. Optimizing management of stage IV EGFR mutant non-small cell lung cancer in Asia: An expert opinion. Int J Cancer. 2025;157(8):1648-1661. doi:10.1002/ijc.35512 各年份药物变化情况表 2022年药物（基准） 2023年变化（相比2022年） 2024年变化（相比2023年） 2025年变化（相比2024年）呼吸系统吉非替尼、厄洛替尼、埃克替尼、阿法替尼、达可替尼、奥希替尼、阿美替尼、伏美替尼、克唑替尼、阿来替尼、塞瑞替尼、恩沙替尼、布格替尼、洛拉替尼、贝伐珠单抗、重组人血管内皮抑制素、安罗替尼、依维莫司、普拉替尼、赛沃替尼、达拉非尼、曲美替尼、恩曲替尼、纳武利尤单抗、帕博利珠单抗、度伐利尤单抗、阿替利珠单抗、卡瑞利珠单抗、替雷利珠单抗、信迪利单抗、伊匹木单抗、舒格利单抗新增：贝福替尼、伊鲁阿克、塞普替尼、谷美替尼、莫博赛替尼、特瑞普利单抗、斯鲁利单抗、派安普利单抗、阿得贝利单抗新增：瑞齐替尼、瑞厄替尼、舒沃替尼、依奉阿克、伯瑞替尼、特泊替尼、卡马替尼、安奈克替尼、瑞普替尼、贝莫苏拜单抗、依沃西单抗新增：利厄替尼、佐利替尼、他雷替尼、氟泽雷塞、格索雷塞、戈来雷塞、德曲妥珠单抗、瑞康曲妥珠单抗、埃万妥单抗、芦康沙妥珠单抗、芦比替定删除：无删除：莫博赛替尼删除：无消化系统索拉非尼、瑞戈非尼、仑伐替尼、多纳非尼、阿替利珠单抗、信迪利单抗、卡瑞利珠单抗、替雷利珠单抗、帕博利珠单抗、特瑞普利单抗、曲妥珠单抗、阿帕替尼、纳武利尤单抗、维迪西妥单抗、雷莫西尤单抗、伊马替尼、舒尼替尼、阿伐替尼、瑞派替尼、依维莫司、索凡替尼、贝伐珠单抗、西妥昔单抗、呋喹替尼、恩沃利单抗、斯鲁利单抗、拉罗替尼、佩米替尼新增：普特利单抗、尼妥珠单抗新增：德曲妥珠单抗、舒格利单抗、卡度尼利单抗、度伐利尤单抗新增：伊匹木单抗、佐妥昔单抗、西妥昔单抗β、恩考芬尼、泽尼达妥单抗删除：拉罗替尼删除：无删除：无血液伊马替尼、达沙替尼、尼洛替尼、奥雷巴替尼、氟马替尼、伊布替尼、泽布替尼、奥布替尼、硼替佐米、卡非佐米、伊沙佐米、沙利度胺、来那度胺、泊马度胺、达雷妥尤单抗、塞利尼索、吉瑞替尼、维奈克拉、艾伏尼布、贝林妥欧单抗、信迪利单抗、卡瑞利珠单抗、替雷利珠单抗、派安普利单抗、利妥昔单抗、奥妥珠单抗、维布妥昔单抗、西达本胺、芦可替尼新增：赛帕利单抗、瑞帕妥单抗、泽贝妥单抗、维泊妥珠单抗、奥加伊妥珠单抗、林普利塞、度维利塞、莫格利珠单抗、司妥昔单抗、伊基奥仑赛、阿基仑赛、瑞基奥仑赛新增：特立妥单抗、戈利昔替尼、泽沃基奥仑赛、格菲妥单抗、罗培干扰素α-2b 新增：泊那替尼、阿思尼布、阿可替尼、匹妥布替尼、艾沙妥昔单抗、塔奎妥单抗、埃纳妥单抗、坦昔妥单抗、吉卡昔替尼、他泽司他、纳基奥仑赛、莫妥珠单抗、埃普奈明删除：无删除：无删除：无泌尿系统索拉非尼、舒尼替尼、培唑帕尼、阿昔替尼、依维莫司、替雷利珠单抗、特瑞普利单抗、维迪西妥单抗、阿比特龙、阿帕他胺、恩扎卢胺、达罗他胺、瑞维鲁胺、奥拉帕利、仑伐替尼、纳武利尤单抗、帕博利珠单抗无新增：伏罗尼布新增：他拉唑帕利、维恩妥尤单抗、安罗替尼、贝莫苏拜单抗、贝组替凡、厄达替尼删除：无删除：无乳腺癌曲妥珠单抗、恩美曲妥珠单抗、帕妥珠单抗、伊尼妥单抗、拉帕替尼、吡咯替尼、奈拉替尼、哌柏西利、阿贝西利、西达本胺、达尔西利、依维莫司、戈沙妥珠单抗新增：德曲妥珠单抗、瑞波西利、帕博利珠单抗新增：帕妥珠曲妥珠单抗（皮下注射）、特瑞普利单抗、恩替司他新增：维迪西妥单抗、芦康沙妥珠单抗、吡洛西利、伏维西利、来罗西利、泰瑞西利、伊那利塞、卡匹色替、阿帕替尼、氟唑帕利、奥拉帕利删除：无删除：无删除：无皮肤维莫非尼、达拉非尼、曲美替尼、帕博利珠单抗、特瑞普利单抗、索立德吉、伊马替尼新增：普特利单抗新增：妥拉美替尼新增：无删除：无删除：无删除：伊马替尼骨与软组织依维莫司、地舒单抗、安罗替尼、拉罗替尼新增：无新增：他泽司他新增：无删除：拉罗替尼删除：无删除：他泽司他头颈部尼妥珠单抗、特瑞普利单抗、卡瑞利珠单抗、索拉非尼、仑伐替尼、安罗替尼、纳武利尤单抗、西妥昔单抗、帕博利珠单抗、替雷利珠单抗、普拉替尼无新增：塞普替尼新增：菲诺利单抗删除：无删除：无生殖系统奥拉帕利、尼拉帕利、氟唑帕利、帕米帕利、贝伐珠单抗、卡度尼利单抗无新增：索卡佐利单抗、赛帕利单抗新增：塞纳帕利、苏维西塔单抗、法米替尼、安罗替尼、恩朗苏拜单抗、艾帕洛利托沃瑞利单抗、帕博利珠单抗、卡瑞利珠单抗、贝莫苏拜单抗、索米妥昔单抗删除：无删除：无泛实体瘤无新增：拉罗替尼、恩曲替尼、恩沃利单抗、替雷利珠单抗、斯鲁利单抗、普特利单抗新增：帕博利珠单抗新增：无删除：无删除：无

2026-03-24

·PRNewswire

Karyopharm's Phase 3 SENTRY Trial in Myelofibrosis Met First Co-Primary Endpoint, Demonstrating Statistically Significant Improvement in Spleen Volume Reduction

– While Similar Symptom Improvement Was Observed Across the Two Arms Relative to Baseline, SENTRY Did Not Meet its Second Co-Primary Endpoint of Abs-TSS – – SENTRY Demonstrated a Rapid and Near Doubling of Patients Achieving SVR35 at Week 24, versus Ruxolitinib – – Promising Overall Survival Signal with >50% Reduction of Risk of Death versus Ruxolitinib – – Evidence of Potential Disease Modification with More Patients Achieving ≥20% Reductions in VAF as Early as Week 24 versus Ruxolitinib – – No New Safety Signals Identified – – Karyopharm will Meet with the FDA to Discuss the Totality of the Data and Potential sNDA Filing – – Conference Call Scheduled for Today at 8:00 a.m. ET – NEWTON, Mass., March 24, 2026 /PRNewswire/ -- Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today reported topline results from its Phase 3 SENTRY trial, a randomized, double-blind, placebo-controlled trial of 60 mg selinexor in combination with ruxolitinib in frontline myelofibrosis (n=353). The trial met the first co-primary endpoint, demonstrating statistically significant improvement in spleen volume reduction of 35% or more (SVR35) for patients treated with the combination of selinexor plus ruxolitinib, with rapid, deep and sustained spleen volume reduction rates seen in the combination arm. The mean change in absolute total symptom score (Abs-TSS) at week 24 relative to baseline was comparable across the two arms with similar symptom improvement relative to baseline; the difference across the two arms was not statistically significant. Importantly, the topline results suggest a promising signal in overall survival (OS) for the combination arm. Spleen Volume: 50% of patients who received the combination of selinexor plus ruxolitinib achieved a statistically significant improvement in SVR35 at week 24 compared to 28% of patients who received ruxolitinib alone (one-sided p<0.0001). Patients on the combination achieved rapid spleen reduction with 49% already achieving SVR35 at week 12 compared to 20% who received ruxolitinib alone. Spleen volume reduction was sustained, with 47% of patients on the combination achieving SVR35 at week 36 compared to 23% who received ruxolitinib alone. Symptoms: Similar symptom improvement from baseline was observed in patients who received the combination of selinexor plus ruxolitinib compared to ruxolitinib alone as measured by Abs-TSS at week 24. Patients who received the combination reported a 9.89 point improvement in Abs-TSS compared to a 10.86 point improvement in patients who received ruxolitinib alone. Overall Survival: Promising OS signal was observed in patients who received the combination of selinexor plus ruxolitinib compared to ruxolitinib alone with a hazard ratio of 0.43 (95% CI [0.19, 1.00] nominal one-sided p=0.0222). The Company intends to continue to follow OS to maturity to further evaluate this signal. Overall Survival Associated with SVR35: Post-hoc landmark analyses at weeks 12 and 24 suggest SVR35 may predict overall survival. Variant Allele Frequency (VAF) Reduction: Evidence of potential disease modification from a pre-specified exploratory endpoint was observed at week 24 from baseline in the combination arm as 32% of patients who received the combination achieved a ≥20% reduction in VAF for JAK2, MPL, and CALR compared to 24% of patients who received ruxolitinib alone (n=261). Other Secondary and Exploratory Endpoints: Across other secondary and exploratory endpoints of progression-free survival, hemoglobin stabilization, and bone marrow fibrosis improvement, no meaningful difference was observed between the trial arms as of the data cut-off of February 20, 2026. The Company intends to further evaluate these endpoints as they mature. Patients were randomized 2:1 to 60 mg of selinexor once weekly plus ruxolitinib or placebo plus ruxolitinib. The ruxolitinib dose was determined based on the patients' baseline platelet count per the drug's prescribing information. All data presented are as of the data cut-off of February 20, 2026. "The results from SENTRY are an important development for patients as the combination of selinexor plus ruxolitinib meaningfully improved spleen response and we observed a promising signal in overall survival. Reducing spleen volume remains one of the most important treatment goals in myelofibrosis since achieving SVR35 is associated with improvement in overall survival," said Dr. John Mascarenhas, Professor of Medicine at the Icahn School of Medicine at Mount Sinai and Director of the Center of Excellence for Blood Cancers and Myeloid Disorders. "While the symptom endpoint did not reach statistical significance, patients treated in both arms achieved similar symptom improvement relative to baseline. Importantly, while JAK inhibitors have been the backbone of therapy, continued progress requires new therapies that target additional biological pathways. Inhibition of XPO1 represents a differentiated mechanism that has the potential to address these pathways and evolve treatment beyond JAK inhibition alone." "For patients with myelofibrosis, improvements in spleen and symptoms are expected outcomes from JAK inhibitors such as ruxolitinib. The SENTRY topline results suggest that the combination of selinexor and ruxolitinib delivers superior spleen reduction, which may predict overall survival, while offering similar symptom improvement, and may offer an important advance for our patients," said Dr. Claire Harrison, Professor of Myeloproliferative Neoplasms and Deputy Chief Medical Officer of Research, Data, and Analytics at Guy's and St. Thomas' NHS Foundation Trust in the United Kingdom. "Selinexor's differentiated mechanism provides a complementary approach to JAK inhibition and highlights the importance of targeting additional biological pathways beyond JAK signaling to further advance outcomes for patients with myelofibrosis. I am encouraged by the speed and magnitude of spleen response, and the promising overall survival signal and evidence of potential disease modification. In totality, these data underscore selinexor's potential to meaningfully improve clinical outcomes for patients with myelofibrosis," said Reshma Rangwala, MD, PhD, Chief Medical Officer and Head of Research of Karyopharm. "On behalf of Karyopharm, I would like to thank the patients, families, caregivers, investigators, and clinical trial team who participated in this trial. We are excited to share our results with regulatory authorities, key opinion leaders and patient advocacy organizations." "The myelofibrosis community is waiting for new treatment options that can build upon the benefit of JAK inhibitors. Improving overall survival is the ultimate goal for people living with myelofibrosis and I am incredibly encouraged by these results," said Kapila Viges, Chief Executive Officer of the MPN Research Foundation. "These results are an exciting development for the myelofibrosis community." Safety and Tolerability The combination demonstrated a manageable safety and tolerability profile consistent with the known profile of selinexor and ruxolitinib individually. No new safety signals were observed. The five most common all-grade treatment emergent adverse events (TEAEs) in the selinexor plus ruxolitinib arm were thrombocytopenia (selinexor plus ruxolitinib arm: 59%; placebo plus ruxolitinib arm: 43%), anemia (57%; 58%), nausea (57%; 17%), constipation (32%; 36%) and neutropenia (27%; 9%) (n=234; n=116). The rate of grade 3+ TEAEs was 70% in the selinexor plus ruxolitinib arm compared to 50% in the placebo plus ruxolitinib arm. The rate of TEAEs leading to treatment discontinuation was 15% in the selinexor plus ruxolitinib arm and 9% in the placebo plus ruxolitinib arm. The rate of confirmed leukemic transformations was the same across both arms of the trial at 1.7%. Next Steps The Company will be meeting with the U.S. Food and Drug Administration (FDA) to discuss the totality of the data from the SENTRY trial and its supplemental new drug application (sNDA) filing plan. The Company plans to share additional data from the Phase 3 SENTRY trial at an upcoming medical meeting and expects to submit a manuscript to a peer-reviewed medical journal. The Company believes that potential inclusion in relevant compendia could occur in the second half of 2026. Conference Call Information Karyopharm will host a conference call today, March 24, 2026, at 8:00 a.m. Eastern Time, to discuss the results of its Phase 3 SENTRY trial in myelofibrosis. To access the conference call, please dial (800) 836-8184 (local) or (646) 357-8785 (international) at least 10 minutes prior to the start time and ask to be joined into the Karyopharm Therapeutics call. A live audio webcast of the call, along with accompanying slides, will be available under "Events & Presentations" in the Investor section of the Company's website. An archived webcast will be available on the Company's website approximately two hours after the event. About the Phase 3 SENTRY Trial SENTRY (XPORT-MF-034; NCT04562389) is a Phase 3 clinical trial evaluating a once-weekly dose of 60 mg of selinexor in combination with ruxolitinib compared to placebo plus ruxolitinib in JAKi-naïve myelofibrosis patients with platelet counts >100 x 10 9/L. Patients were randomized 2-to-1 to the selinexor arm. The co-primary endpoints for this trial are spleen volume reduction ≥ 35% (SVR35) at week 24 and the average change in absolute total symptom score (Abs-TSS) over 24 weeks relative to baseline. About Myelofibrosis Myelofibrosis is a rare blood cancer that affects approximately 20,000 patients in the United States and 17,000 patients in the European Union1. The disease causes bone marrow fibrosis (scarring in the bone marrow), which makes it difficult for the bone marrow to make healthy blood cells, splenomegaly (enlarged spleen), progressive anemia which often leads to symptoms like fatigue and weakness, and other disease associated symptoms including abdominal discomfort, pain under the left ribs, early satiety, night sweats and bone pain. The only approved class of therapies to treat myelofibrosis are JAK inhibitors, including ruxolitinib. About XPOVIO® (selinexor) XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor compound for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved in the U.S. and marketed by Karyopharm in multiple oncology indications, including: (i) in combination with VELCADE® (bortezomib) and dexamethasone (XVd) in adult patients with multiple myeloma after at least one prior therapy; (ii) in combination with dexamethasone in adult patients with heavily pre-treated multiple myeloma; and (iii) under accelerated approval in adult patients with diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. XPOVIO® (also known as NEXPOVIO® in certain countries) has received regulatory approvals in various indications in a growing number of ex-U.S. territories and countries, including but not limited to the European Union, the United Kingdom, Mainland China, Taiwan, Hong Kong, Australia, South Korea, Singapore, Israel, and Canada. XPOVIO®/NEXPOVIO® is marketed in these respective ex-U.S. territories by Karyopharm's partners: Antengene, Menarini, Neopharm, and FORUS. Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high unmet need cancer indications, including in myelofibrosis and endometrial cancer. For more information about Karyopharm's products or clinical trials, please contact the Medical Information department at: Tel: +1 (888) 209-9326; Email: [email protected] XPOVIO® (selinexor) is a prescription medicine approved: In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd). In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti‐CD38 monoclonal antibody (Xd). For the treatment of adult patients with relapsed or refractory diffuse large B‐cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). SELECT IMPORTANT SAFETY INFORMATION Warnings and Precautions Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care. Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony‐stimulating factors. Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care. Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care. Serious Infection: Monitor for infection and treat promptly. Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes. Embryo‐Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception. Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract. Adverse Reactions The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3‐4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%. The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%. The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3‐4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions was infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection (21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients. Use In Specific Populations Lactation: Advise not to breastfeed. For additional product information, including full prescribing information, please visit . To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1‐888‐209‐9326 or FDA at 1‐800‐FDA‐1088 or . About Karyopharm Therapeutics Karyopharm Therapeutics Inc. (Nasdaq: KPTI) is a commercial-stage pharmaceutical company whose dedication to pioneering novel cancer therapies is fueled by a belief in the extraordinary strength and courage of patients with cancer. Since its founding, Karyopharm has been an industry leader in oral compounds that address nuclear export dysregulation, a fundamental mechanism of oncogenesis. Karyopharm's lead compound and first-in-class, oral exportin 1 (XPO1) inhibitor, XPOVIO® (selinexor), is approved in the U.S. and marketed by the Company in three oncology indications. It has also received regulatory approvals in various indications in 50 ex-U.S. territories and countries, including the European Union, the United Kingdom (as NEXPOVIO®) and China. Karyopharm has a focused pipeline targeting indications in multiple high unmet need cancers, including in multiple myeloma, endometrial cancer, myelofibrosis, and diffuse large B-cell lymphoma (DLBCL). For more information about our people, science and pipeline, please visit , and follow us on LinkedIn and on X at @Karyopharm. Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding the ability of selinexor to treat patients with multiple myeloma, endometrial cancer, myelofibrosis, diffuse large B-cell lymphoma and other diseases; expectations with respect to the clinical development plans, regulatory discussions and potential regulatory submissions for selinexor; and expectations regarding the timing, presentation and publication of additional data from the Phase 3 SENTRY trial. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond Karyopharm's control, that may cause actual events or results to differ materially from Karyopharm's current expectations. For example, there can be no guarantee that Karyopharm will successfully commercialize XPOVIO or that any of Karyopharm's drug candidates, including selinexor, will successfully complete necessary clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in the development or commercialization of Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the adoption of XPOVIO in the commercial marketplace, the timing and costs involved in commercializing XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; the ability to obtain and retain regulatory approval of XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; Karyopharm's results of clinical trials and preclinical trials, including subsequent analysis of existing data and new data received from ongoing and future trials; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical trials; the ability of Karyopharm or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the potential future financial implications of such agreement; Karyopharm's ability to enroll patients in its clinical trials; unplanned cash requirements and expenditures; substantial doubt exists regarding Karyopharm's ability to continue as a going concern; development or regulatory approval of drug candidates by Karyopharm's competitors for products or product candidates in which Karyopharm is currently commercializing or developing; and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual property protection for any of its products or product candidates. These and other risks are described under the caption "Risk Factors" in Karyopharm's Annual Report on Form 10-K for the year ended December 31, 2025, which was filed with the Securities and Exchange Commission (SEC) on February 13, 2026, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and, except as required by law, Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. XPOVIO® and NEXPOVIO® are registered trademarks of Karyopharm Therapeutics Inc. SOURCE Karyopharm Therapeutics Inc. 21% more press release views with Request a Demo

临床结果临床3期上市批准加速审批

100 项与硼替佐米相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D03150	硼替佐米	L01XX32	DB00188

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
免疫球蛋白轻链淀粉样变性	日本	Janssen Pharmaceutical KK	2006-10-20
巨球蛋白血症	日本	Janssen Pharmaceutical KK	2006-10-20
套细胞淋巴瘤	欧盟	Janssen-Cilag International NV	2004-04-26
套细胞淋巴瘤	冰岛	Janssen-Cilag International NV	2004-04-26
套细胞淋巴瘤	列支敦士登	Janssen-Cilag International NV	2004-04-26
套细胞淋巴瘤	挪威	Janssen-Cilag International NV	2004-04-26
多发性骨髓瘤	美国	Takeda Pharmaceuticals U.S.A., Inc.	2003-05-13

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
血液肿瘤	临床3期	芬兰	Celgene Corp.	2015-03-18
复发性弥漫性大B细胞淋巴瘤	临床3期	意大利	Janssen-Cilag Ltd.	2013-02-04
复发性弥漫性大B细胞淋巴瘤	临床3期	意大利	Janssen Pharmaceutica NV	2013-02-04
难治性弥漫性大 B 细胞淋巴瘤	临床3期	意大利	Janssen Pharmaceutica NV	2013-02-04
难治性弥漫性大 B 细胞淋巴瘤	临床3期	意大利	Janssen-Cilag Ltd.	2013-02-04
浆细胞白血病	临床3期	中国	Janssen Scientific Affairs LLC	2012-01-13
浆细胞白血病	临床3期	澳大利亚	Janssen Scientific Affairs LLC	2012-01-13
浆细胞白血病	临床3期	韩国	Janssen Scientific Affairs LLC	2012-01-13
弥漫性大B细胞淋巴瘤	临床3期	瑞士	Janssen-Cilag Ltd.	2011-04-01
弥漫性大B细胞淋巴瘤	临床3期	英国	Janssen-Cilag Ltd.	2011-04-01

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01919086 (CTgov)	临床2期	多发性骨髓瘤	30	Lenalidomide+Bortezomib+Dexamethasone	觸餘製窪獵鑰築憲壓鹹 = 簾範廠艱醖鏇襯繭夢顧積淵膚願鬱構鬱膚壓願 (願壓鹹夢鏇繭餘鬱積鬱, 糧構壓願鏇願窪簾鏇廠 ~ 醖襯鹹膚夢鏇鑰廠簾鏇) 更多	-	2026-03-02
NCT02553460 (Pubmed \| Lancet Haematol)	临床1/2期	急性淋巴细胞白血病 KMT2A rearranged	50	BortezomibDexamethasoneVorinostatMitoxantronePegaspargase + BortezomibDexamethasoneVorinostatMitoxantronePegaspargase + BortezomibDexamethasoneVorinostatMitoxantronePegaspargasee + BortezomibDexamethasoneVorinostatMitoxantronePegaspargase + BortezomibDexamethasoneVorinostatMitoxantronePegaspargase	壓遞糧顧鹹艱醖築獵構(鏇膚襯淵窪築餘餘襯顧) = 廠鹽鏇廠獵齋餘蓋顧範鹹築淵鹽構艱積積網廠 (憲衊觸襯築廠糧膚糧壓 )	积极	2026-03-01
NCT03850366 (Tandem Meetings ASTCT and CIBMTR2026)	临床2期	外周干细胞移植	9	Fludarabine+Melphalan+TBI200 cGy+Haplo-SCT+PTCY+Bortezomib (Hematologic Malignancies)	壓鹽壓夢餘窪鹽鬱範構(廠範願膚糧夢蓋鏇獵蓋) = Six patients had cytokine release syndrome (CRS) with ASTCT grade of 1. Four patients had neutropenic fever, and one patient had engraftment fever. Median neutrophils and platelets engraftment were 16 and 26 days respectively. Two patients had reactivation of CMV, 2 had EBV, one had adenovirus, 3 had HHV6, all resolved. At 1 year for 7 evaluable patients IgG were >400 mg/dl and CD4 > 200 cells/ul. 鏇鹽鏇鏇築夢顧築鏇餘 (願製築遞鹽簾積壓構鑰 ) 更多	积极	2026-02-04
Tandem Meetings ASTCT and CIBMTR2026	临床1/2期	移植物抗宿主病	57	Post-transplant cyclophosphamide 50mg/kg (Full dose PTC)	鬱襯鏇構淵構鬱壓構獵(窪製觸築衊鹹糧繭顧構) = 1 patient developed PTLD, responsive to rituximab 膚鏇積餘積製獵衊醖襯 (繭膚鑰願鑰鹹鏇觸壓廠 ) 更多	积极	2026-02-04
				Post-transplant cyclophosphamide 37.5mg/kg (Reduced dose PTC)
Tandem Meetings ASTCT and CIBMTR2026	N/A	多发性骨髓瘤	71	Daratumumab+Bortezomib+Lenalidomide+Dexamethasone	衊廠憲鬱願鏇選襯觸襯(窪鬱鑰廠糧醖願齋觸繭) = 積遞廠齋顧鬱觸淵壓廠鏇夢積顧衊選構膚鹹顧 (鬱範衊選鑰蓋蓋襯窪積 ) 更多	积极	2026-02-04
				Daratumumab+Bortezomib+Lenalidomide+Dexamethasone (2025 IMS/IMWG high-risk criteria)	衊廠憲鬱願鏇選襯觸襯(窪鬱鑰廠糧醖願齋觸繭) = 衊積築壓願觸築齋餘鹽鏇夢積顧衊選構膚鹹顧 (鬱範衊選鑰蓋蓋襯窪積 ) 更多
Tandem Meetings ASTCT and CIBMTR2026	N/A	多发性骨髓瘤	140	Daratumumab+ bortezomib/cafilzomib+ lenalidomide+ dexamethasone (CD34+ cells <5×10^6/kg)	網艱鹽艱憲醖選艱壓鹹(膚夢製衊襯選廠醖壓衊) = 範鹹膚鹹鬱鬱簾壓齋簾淵網鬱繭壓選淵衊廠窪 (獵醖製積淵獵蓋鹹簾蓋 ) 更多	积极	2026-02-04
				Daratumumab+ bortezomib/cafilzomib+ lenalidomide+ dexamethasone (CD34+ cells ≥5×10^6/kg)	網艱鹽艱憲醖選艱壓鹹(膚夢製衊襯選廠醖壓衊) = 鬱觸製膚築糧鑰餘範窪淵網鬱繭壓選淵衊廠窪 (獵醖製積淵獵蓋鹹簾蓋 ) 更多
ASH2025	N/A	多发性骨髓瘤一线	1,085	CyBorD	選窪鬱簾蓋艱壓夢夢齋(鏇襯觸膚廠廠壓鹽築壓) = 築壓築廠鏇夢膚艱選製廠憲淵觸網夢廠醖範襯 (鬱製壓齋廠廠遞鹽顧積, 8.6 ~ 15.4) 更多	积极	2025-12-06
				Rd	選窪鬱簾蓋艱壓夢夢齋(鏇襯觸膚廠廠壓鹽築壓) = 醖廠觸築積鹹憲淵壓網廠憲淵觸網夢廠醖範襯 (鬱製壓齋廠廠遞鹽顧積, 10.9 ~ 19.3) 更多
ASH2025	N/A	多发性骨髓瘤一线	152	MRD guided consolidation with VRd/KPd	齋鑰淵願鏇醖衊夢艱蓋(艱衊艱齋獵餘襯糧鹽範) = 淵積襯齋鹽製鹹鏇築製構觸憲憲鏇鑰繭築鹹選 (鬱醖鏇衊膚夢衊廠顧鏇 ) 更多	积极	2025-12-06
ASH2025	N/A	肾功能不全一线	68	iCyBorD regimen	餘選願艱選壓齋憲願鹹(膚遞鑰艱積鏇蓋觸遞築) = 簾顧壓構壓醖構積積選夢繭壓鏇獵醖鏇糧築醖 (簾鑰襯選鹽觸夢憲淵觸 ) 更多	积极	2025-12-06
				CyBorD	餘選願艱選壓齋憲願鹹(膚遞鑰艱積鏇蓋觸遞築) = 淵鑰憲範糧壓窪範繭蓋夢繭壓鏇獵醖鏇糧築醖 (簾鑰襯選鹽觸夢憲淵觸 ) 更多
ChiCTR2200064695 (ASH2025)	临床2期	肾功能不全一线	63	Selinexor + Pomalidomide + Bortezomib + Dexamethasone	糧鏇範顧繭膚簾鹽膚簾(膚鹽觸網範鏇憲觸獵窪) = 醖襯憲夢蓋願膚夢醖襯糧範選壓餘襯窪齋顧蓋 (醖齋簾壓範鏇齋淵淵鹽 ) 更多	积极	2025-12-06