Multiple myeloma (MM) is a plasma cell disease characterized by the growth of clonal plasma cells in the bone marrow. The purpose of this study is to assess the adverse events and change in disease activity of etentamig in combination with a cereblon E3 ligase modulatory drug (CELMoD) agent in adult participants with relapsed/refractory (R/R) multiple myeloma (MM). Adverse events and change in disease state will be assessed.
Etentamig is an investigational drug being developed for the treatment of R/R MM. Study doctors put the participants in groups called treatment arms. Multiple doses of etentamig in combination with iberdomide will be explored. Each treatment arm receives a different dose of etentamig and iberdomide to determine a tolerable dose. Approximately 135 adult participants with R/R MM will be enrolled in the study in approximately 50 sites worldwide.
In phase 1 participants will receive escalating intravenous (IV) etentamig in combination with oral iberdomide. In phase 2 participants will receive IV etentamig at one of two doses in combination with oral iberdomide, as part of the approximately 129 month study duration.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and and monitoring of side effects.

开始日期2025-08-07

申办/合作机构

AbbVie, Inc.

NCT06348108

/ Recruiting临床1期IIT

A Phase Ib, Multi-center, Study of Talquetamab in Combination With Iberdomide and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma

This phase I trial will evaluate the safety, side effects, and best dose of talquetamab in combination with iberdomide and dexamethasone in treating patients with multiple myeloma that has come back after a period of improvement (relapsed) or has not responded to previous treatment (refractory). There is currently a significant unmet need for patients with relapsed or refractory multiple myeloma (RRMM) who are triple class refractory and have been exposed to B-cell maturation antibody (BCMA) targeted therapy. These patients currently have limited treatment options and poor survival. Talquetamab is an FDA approved drug that can bring T-cells to the myeloma cell, resulting in myeloma cell death. Iberdomide is an investigational drug and works by targeting and destroying proteins that help myeloma cancer cells to survive. Dexamethasone is a corticosteroid, is similar to a natural hormone produced by the adrenal glands to reduce inflammation (swelling, heat, redness, and pain) and is used to in helping to treat certain types of cancer including myeloma.

开始日期2025-07-28

申办/合作机构

The University of California, San Francisco

[+2]

NCT06762769

/ Recruiting临床2期IIT

Isatuximab and Iberdomide as Immunotherapy for High Risk in Smouldering Myeloma

The study will test a new combination of 3 drugs: Isatuximab (Isa), Iberdomide (Iber) and Dexamethasone (Dex), in patients who have intermediate or high risk smouldering myeloma. Smouldering myeloma is an early form of myeloma which may progress to active multiple myeloma, but at a slow rate. Patients with smouldering myeloma do not usually receive any treatment but will have regular check-ups and observation. Some patients have a diagnosis of smouldering myeloma which has a higher risk of progressing to active myeloma.
The study will test if the combination of drugs is effective at preventing or delaying the disease progressing into active multiple myeloma. The study will also test if the combination is tolerated and accepted by patients.

开始日期2025-06-02

申办/合作机构

University College London

[+2]

100 项与伊伯多胺相关的临床结果

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100 项与伊伯多胺相关的转化医学

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100 项与伊伯多胺相关的专利（医药）

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项与伊伯多胺相关的文献（医药）

2026-01-01·Lancet Haematology

Iberdomide plus low-dose cyclophosphamide and dexamethasone in patients with relapsed and refractory multiple myeloma (the ICON study): a multicentre, single-arm, phase 2 trial

Article

作者: Roeloffzen, Wilfried W H ; Verkleij, Christie P M ; de Ruijter, Maaike E M ; Wegman, Jurgen ; Zweegman, Sonja ; Nijhof, Inger S ; Smits, Febe ; de Weerdt, Okke ; Nasserinejad, Kazem ; Kerstiens, Ramses ; Smit, Nina ; Franssen, Laurens E ; Mutis, Tuna ; de Kort, Elizabeth A ; Korst, Charlotte L B M ; Croockewit, Alexandra J ; van de Donk, Niels W C J ; Levin, Mark-David ; Plattel, Wouter ; van der Spek, Ellen ; van der Klift, Marjolein ; Groen, Kaz ; Westerman, Matthijs

BACKGROUND:

Iberdomide is an oral cereblon E3 ligase modulator with higher affinity to cereblon than immunomodulatory drugs, leading to improved direct anti-myeloma activity and enhanced immunostimulatory effects. We aimed to evaluate the safety and activity of iberdomide plus low-dose cyclophosphamide and dexamethasone (IberCd) in patients with relapsed and refractory multiple myeloma.

METHODS:

The ICON study is a prospective, single-arm, phase 2, open-label study conducted in eight hospitals in the Netherlands. We enrolled patients (aged ≥18 years) with relapsed and refractory multiple myeloma (lenalidomide-refractory) who had received two to four previous lines of therapy and had a WHO performance status of 0-2. Patients were treated with oral iberdomide (1·6 mg/day on days 1-21 of each 28-day cycle), oral low-dose cyclophosphamide (50 mg/day on days 1-28), and oral dexamethasone (40 mg [20 mg in patients age >75 years] once a week) until progression. All patients received thrombosis prophylaxis daily: 80 mg oral aspirin or 100 mg oral carbasalate calcium. Patients with a previous history of venous thromboembolism received only low molecular-weight heparin by subcutaneous injection. The primary endpoint was progression-free survival, defined as time from the start of treatment to the date of progression or death. Activity and safety were assessed in all patients who started treatment. This trial was registered at ClinicalTrials.gov (NCT04392037) and is ongoing.

FINDINGS:

Between Feb 17, 2021, and July 7, 2023, 61 patients were enrolled and received IberCd treatment (29 [48%] were female and 32 [52%] patients were male). The median number of previous lines of therapy was 3 (range 2-5); 52 (85%) patients were triple-class exposed and 27 (44%) had triple-class refractory disease. 50 patients discontinued study treatment, 39 of whom due to progressive disease, but all 61 patients were included in the main analysis population. After a median follow-up of 25·4 months (IQR 19·7-31·6), the median progression-free survival was 17·6 months (one-sided 95% CI 16·6-19·9). In all 61 patients, the most common grade 3-4 adverse events were neutropenia (34 [56%] patients) and infections (21 [34%] patients). Treatment-related serious adverse events were reported in 25 (41%) patients, with infections being the most common (34 [71%] of 48 serious adverse events). Treatment-related death occurred in one (2%) patient due to COVID-19.

INTERPRETATION:

IberCd is an all-oral and active combination for patients with relapsed and refractory multiple myeloma that showed clinically meaningful activity. This regimen offers a valuable treatment option for patients who have received two to four previous lines of therapy and compares favourably with other available treatments.

FUNDING:

Bristol Myers Squibb.

2025-12-18·BLOOD

An immunostimulatory CELMoD combination overcomes resistance to T-cell engagers caused by a high multiple myeloma burden

Article

作者: Chesi, Marta ; Meermeier, Erin W. ; Pfeffer, Kirsten ; Sharik, Meaghen E. ; Bergsagel, P. Leif ; Zhu, Yuan Xiao ; Tafoya Alvarado, Yuliza ; Shi, Chang-Xin ; Du, Megan T. ; Stein, Caleb K.

Abstract:

Bispecific T-cell engagers (TCEs) targeting B-cell maturation antigen (BCMA) and CD3, induce deep hematologic responses in ∼60% of heavily pretreated patients with multiple myeloma (MM). We and others found that high tumor burden leads to resistance to TCE and novel strategies are urgently needed to improve responses in this setting. Ikaros degraders, including immunomodulatory drugs (IMiDs) and cereblon E3 ligase modulatory drugs (CELMoDs), represent logical partners for TCEs due to their direct anti-MM effects and additional immune-stimulatory activity; however, it is unclear how to optimally combine them with TCEs. Taking advantage of the immunocompetent IMiD-sensitive Vk∗MYChCRBN murine model of MM, we optimized strategies to overcome primary resistance to BCMA-TCEs and achieve sustained remission, while maintaining a manageable safety profile. The addition of anti–programmed cell death protein 1 (PD1) and pomalidomide reduced the T-cell exhaustion that occurs in response to TCEs in high tumor burden settings. This allowed for a higher degree of T-cell activation and significant improvement in response rates but also increased risk of lethal cytokine release syndrome (CRS). To moderate the response and prevent CRS, we evaluated Ikaros degraders and dexamethasone (DEX) with step-up–dosed TCEs. Pretreatment with iberdomide and DEX reshaped the bone marrow T-cell compartment, promoted infiltration of naïve T cells, and generated 100% response rates and the longest survival in subjects with high tumor burden. This was accompanied by more favorable T-cell profiling, with limited expansion of regulatory T cells and exhaustion. Overall, administering a TCE after DEX and iberdomide treatments provided deeper and more durable responses with a reduced risk of CRS.

2025-08-01·JOURNAL OF MEDICAL VIROLOGY

Novel Cereblon‐Binding Immunomodulators Have Increased Potency Against Gammaherpesvirus‐ Associated Lymphomas In Vitro

Article

作者: Davis, David A. ; Shrestha, Prabha ; Treco, Emma N. ; Yarchoan, Robert

ABSTRACT:

Primary effusion lymphoma (PEL), which is caused by Kaposi sarcoma herpesvirus (KSHV), and Burkitt lymphoma (BL), a subset of which are associated with Epstein‐Barr virus (EBV), are aggressive non‐Hodgkin's lymphomas. Both have relatively poor survival compared to other lymphomas. Cereblon‐binding immunomodulators (CBIs), such as pomalidomide (Pom), show in vitro efficacy and clinical activity against certain of these lymphomas. Next generation CBIs, such as golcadomide (Golc) and iberdomide (Iber), have increased affinity to the primary cellular target, cereblon, making them potentially better anticancer agents. Here, we report the in vitro activity of these novel CBIs against PEL and BL cell lines. Both Golc and Iber, but primarily Golc, caused substantial growth suppression of PEL and BL lines with much lower half‐maximal inhibitory concentration (IC50) compared to Pom. This growth suppression was mediated, in part, by enhanced downregulation of interferon regulatory factor 4 (IRF4) in PEL cell lines. Additionally, both Golc and Iber increased immune surface markers such as ICAM‐1, B7‐2, and MHC‐I in PEL and BL cells at lower concentrations than Pom; these increases led to enhanced recognition of both PEL and BL cells by T‐cells. The novel CBIs had relatively little activity in Pom‐resistant cell lines with low levels of cereblon, suggesting that binding to cereblon is also important for the functions of the novel CBIs. These data show that the newer CBIs are more potent and effective against PEL and BL lines than Pom, and therefore, are worth investigating clinically in patients with these tumors.

148

项与伊伯多胺相关的新闻（医药）

2026-01-27

·靶点周知

百时美施贵宝（BMS）血液肿瘤管线深度解码：以创新为炬，拓界价值新程

若您深耕创新药企赛道，专注于管线价值的深度解构、发展逻辑的系统研判与投资潜力的前瞻预判，欢迎私信垂询。我们将以公开信息为基，精研核心数据、梳理发展脉络、预判行业风向，为您的专业决策赋能。在血液肿瘤诊疗技术迭代升级的浪潮中，百时美施贵宝（Bristol Myers Squibb, BMS）以管线布局为根脉，以前沿创新为羽翼，构筑起覆盖多元疾病谱系、贯穿全诊疗周期的核心竞争壁垒。从蛋白降解疗法的突破性跨越，到贫血相关疾病治疗的格局重塑，再到细胞疗法的精准化深耕，BMS血液肿瘤管线凭扎实的科研底蕴与卓越的临床潜力，成为全球药企在该领域布局的标杆典范。蛋白降解疗法：破耐药之桎梏，启诊疗之新章蛋白降解技术作为近年生物医药领域的创新瑰宝，已然成为BMS突破血液肿瘤传统治疗局限的核心利器。公司精心构建的CELMoD药物矩阵及BCL6配体导向降解剂（LDD）管线，精准叩击传统疗法难以触及的治疗靶点，在多发性骨髓瘤、淋巴瘤等核心适应症中，绽放出颠覆性的临床应用光芒。在多发性骨髓瘤领域，三款核心CELMoD药物形成梯次递进的布局态势，全面覆盖疾病不同诊疗阶段的临床诉求。其中，Iberdomide凭借抗肿瘤与免疫调节的双重效能，在不适合造血干细胞移植的新诊断患者中斩获亮眼临床成效，不仅使超半数患者达成微小残留病（MRD）阴性的完全缓解，更在首个治疗周期便彰显出快速、持久的肿瘤抑制效能；针对自体造血干细胞移植后的维持治疗场景，该药物可有效深化缓解深度，MRD转阴率趋近五成，且肾功能损害患者无需调整剂量，让获益人群进一步拓宽。 Mezigdomide聚焦复发/难治性多发性骨髓瘤的诊疗困局，即便面对伴高危分子特征或对传统免疫调节剂耐药的患者群体，仍能高效诱导靶向蛋白降解，触发明确的临床应答。其联合治疗方案在复发/难治患者中初步呈现出优异的缓解率，同时依托与其他疗法的协同探索，持续拓宽血液肿瘤治疗的边界，为疑难病例点亮希望之光。在淋巴瘤领域，Golcadomide堪称该领域的革新之力，为疾病治疗开辟全新路径。在初治侵袭性B细胞淋巴瘤患者中，其联合标准治疗方案的完全代谢缓解率逼近九成，24个月无进展生存率与总生存率均表现卓越，且在高危亚组患者中依旧保持稳定的治疗效能；针对经多线治疗的复发/难治性淋巴瘤患者，该药物仍能实现可观的缓解率与持久的疗效应答，为临床未被满足的需求注入强劲动力。此外，同类首创的BCL6-LDD药物BMS-986458，在复发/难治性非霍奇金淋巴瘤单药治疗中，整体缓解率超七成，与其他疗法的联合应用更释放出强劲的协同效应，为淋巴瘤精准诊疗添砖加瓦。跨域布局贫血领域：靶向核心机制，惠及多元临床场景 BMS血液肿瘤管线的价值版图，并未局限于恶性血液肿瘤领域，更向贫血相关重大疾病诊疗领域延伸，精准锚定临床核心需求实现技术突破。其核心药物通过精准抑制转化生长因子-β（TGF-β）超家族配体，高效促进红系造血细胞的分化与成熟，同步实现造血三系功能的协同改善，从机制根源上破解造血衰竭相关疾病的治疗困局。在骨髓增生异常综合征这一贫血相关核心适应症中，该药物的临床价值持续得到验证与深化。临床数据印证，早期启动该药物治疗，可显著提升患者的长期生存获益，为这类发病机制复杂、治疗手段有限的疾病，提供了稳定可靠的治疗选择，亦彰显出BMS跨疾病领域布局的战略远见与科研担当。细胞疗法与协同治疗：多维攻坚赋能，筑牢领先根基除深耕蛋白降解疗法与贫血治疗领域外，BMS以细胞疗法为重要战略支点，联动多疗法协同应用策略，构筑起全方位、立体化的血液肿瘤治疗体系。长期临床数据印证，其在细胞疗法领域的核心产品，可为淋巴瘤患者带来持久的生存获益，成为复发/难治性淋巴瘤诊疗中的关键支撑。尤为值得关注的是，BMS始终深耕多疗法协同治疗的探索与验证。无论是CELMoD药物与双特异性抗体、CAR-T疗法的联合应用，还是BCL6-LDD药物与其他抗肿瘤疗法的协同攻关，皆通过作用机制的互补叠加，实现临床疗效的跨越式提升。这不仅放大了单一疗法的临床效能，更拓宽了管线的适用场景与人群覆盖，进一步夯实了其在血液肿瘤治疗领域的全球领先地位。管线核心价值总结：广度、深度与创新性的三重赋能 BMS血液肿瘤管线的核心竞争力，源于疾病覆盖广度、研发探索深度与技术创新维度的三重协同赋能。从疾病覆盖来看，管线全面囊括多发性骨髓瘤、白血病、淋巴瘤等恶性血液肿瘤，同时延伸至骨髓增生异常综合征等非恶性血液疾病，实现诊疗全周期的无缝覆盖；从研发深度来看，管线形成“后期成熟品种稳落地、中期核心品种强推进、前期创新分子勇探索”的梯度布局，保障研发成果的持续转化与迭代；从创新维度来看，以蛋白降解技术、细胞疗法为代表的前沿技术应用，突破传统治疗的技术瓶颈，为临床未被满足的需求提供了全新的解决方案。 1）免责声明本文基于百时美施贵宝（BMS）公开报告及相关研究资料整理编撰，仅用于专业信息交流之目的，不构成任何投资建议、诊疗指导或用药依据。临床用药请严格遵循诊疗指南及医师专业医嘱，切勿自行用药。若本文内容存在侵权情形，敬请及时联系我方，我方将依法依规妥善处置。 2）报告获取提示本文为BMS血液肿瘤管线概览性解析，如需原始研究报告，敬请关注本公众号并留言索取。 3）检索词 #百时美施贵宝#BMS#血液肿瘤#管线布局#蛋白降解疗法#细胞疗法#贫血治疗#骨髓增生异常综合征 4）核心结论速览 1. BMS血液肿瘤管线全域覆盖恶性与非恶性血液疾病诊疗全周期，布局前瞻且周全；2. 蛋白降解疗法为核心创新引擎，精准突破传统治疗耐药瓶颈，临床数据坚实有力；3. 跨域布局贫血治疗领域，靶向核心发病机制，填补临床诊疗空白；4. 以细胞疗法为核心，强化多疗法协同攻坚，管线梯队完备，核心竞争优势凸显。

2026-01-26

·药事纵横

“诺奖含金量”的新兑现：靶向蛋白降解疗法CELMoD，指向MM治疗新基石

上个月底，国家药品审评中心（CDE）官网公示，多发性骨髓瘤（MM）领域的靶向蛋白降解药物iberdomide拟被纳入优先审评程序，拟定适应症为：联合达雷妥尤单抗和地塞米松适用于治疗既往接受过至少1线治疗的多发性骨髓瘤成人患者；本月，该药物已正式获优先审评资格。图片来源：CDE官网靶向蛋白降解是近年来药物研发的热门领域，iberdomide（以下简称：IBER）所属的CELMoD平台是目前多发性骨髓瘤领域进展领先的全新靶向蛋白降解剂。CELMoD药物的作用机制借助了2004年诺贝尔化学奖解揭示的“生理性蛋白降解”功能。尽管当时业界已意识到这一生理机制的治疗潜力，但直到以CELMoD药物为代表的新型靶向蛋白降解剂问世，才真正通过理性设计，实现了对特定致病蛋白的靶向降解，为突破“不可成药”的壁垒提供了新的可能。 CELMoD药物在临床层面的进展也在同步持续推进。2025美国血液学会（ASH）年会上公布的多项早期临床结果显示，CELMoD药物在不同类型的多发性骨髓瘤患者中均可观察到深度的缓解，并在联合多种疗法时表现出协同潜力，为其在多发性骨髓瘤治疗体系中的进一步探索提供了依据。众所周知，MM目前仍是不可治愈的疾病，多数患者最终会出现复发与耐药，经历反复“复发-缓解”的恶性循环，且随着治疗线数的增加，患者无进展生存期（PFS）明显缩短[1-3]。因此，延长患者在相对早线治疗阶段的控制时间，是目前MM临床决策的关键目标。这一目标的实现，核心之一在于获得更深度的缓解。也正因此，微小残留病（MRD）阴性作为目前MM最深缓解程度的疗效评价手段，在MM临床治疗中的地位日益凸显：大量研究均已证实MRD阴性与PFS等长期预后指标显著相关。而要取得更深的疾病缓解，则离不开作用机制更为精准的药物。在MM的发生发展中，多种关键致病蛋白（如Ikaros、Aiolos）是MM细胞生存和免疫调控的关键转录因子，通过传统手段难以抑制其活性，即具有“不可成药性”：如果对Ikaros/Aiolos蛋白降解的深度和特异性不足[4]，会限制整体治疗效果。靶向蛋白降解是一类利用人体自身泛素-蛋白酶体系统实现清除致病蛋白的创新机制。这一思路利用了2004年诺贝尔化学奖揭示的基础机制：泛素介导的蛋白质降解是细胞维持稳态的重要生理功能；基于此，学术界意识到，若能对该过程进行精准调节，或可为传统“不可成药”的靶点打开新的治疗通道。而CELMoD药物正是对这一机制的药物化实现。通过精准调节E3泛素连接酶复合物中负责底物识别的核心环节——CRBN，CELMoD药物可强化其底物识别能力，实现对关键致病蛋白Ikaros和Aiolos的高效、选择性降解。这种深度降解机制具备双重抗肿瘤作用：一方面可直接杀伤骨髓瘤细胞，另一方面还具有免疫刺激作用，能增强T细胞和NK细胞功能，实现更强的抗肿瘤免疫反应。从药理学层面来看，CELMoD药物的核心优势在于其可高效形成稳定的CELMoD-CRBN-靶蛋白三元复合物，以实现对Ikaros和Aiolos的强效降解。此外，CELMoD药物以单一S-异构体形式给药，可提供近100%活性成分，确保体内药效稳定，在增强疗效的同时可能降低非靶向效应带来的安全性风险。不仅如此，由于CELMoD药物具有免疫刺激的作用，使其与依赖免疫效应的现有MM疗法，如抗CD38单抗、CAR-T等，均展现出良好的协同效应[5-7]。 ASH作为血液肿瘤领域最受关注的学术会议之一，此前的2025年大会上公布了多项IBER（CELMoD药物之一）的相关临床研究，不仅展现了其实现高比例、持久MRD阴性的潜力，同时在联合新型疗法中表现出强大的协同作用，以及良好的安全性。 01 ASH一线信号：深度缓解目标逐步扩展随着创新疗法的不断应用，MM的治疗目标正向MRD持续阴性等更深层次的缓解迈进。本次ASH大会上公布的两项研究显示，CELMoD药物在不同阶段MM中均展现了MRD阴性缓解方面的优势：在新诊断MM患者中，一项 IBER联合达雷妥尤单抗和地塞米松（IberDd）治疗不适合移植的新诊断多发性骨髓瘤的研究（CC-220-MM-001）[8]显示，该联合方案可诱导高比例且持久的MRD阴性缓解：高达53.3%的患者在任意时间点达到MRD阴性完全缓解（CR）[8]。而在RRMM患者中，另一项II期ReKInDLE研究[9]显示， IBER、卡非佐米、达雷妥尤单抗和地塞米松（IberKDd）四药联合方案在早线复发MM中疗效可观：在可评估患者中，62.5%的患者达到MRD阴性CR，且不良反应总体可控。以上研究提示，CELMoD药物的联合方案可诱导高比例、持久MRD阴性缓解，提示其可能改善现有药物缓解较短暂、易复发的痛点，带来更佳的长期预后。 02 治疗边界的延展：肾功能不全不再构成“壁垒” 肾功能不全是MM患者的常见并发症，约20%~50%的患者会在MM进程中出现肾功能不全[10]，伴肾功能不全的患者往往预后更差，临床治疗面临挑战。CC-220-MM-001研究亚组分析[11]显示，接受IberDd方案治疗的患者，无论肾损伤程度如何，其疗效（ORR、≥CR）和安全性均无显著差异，且肾损伤状态不影响IBER的清除率。这一发现提示轻、中度肾功能损伤患者无需调整IBER的剂量，有望为该类特殊人群的治疗带来有效、安全性良好的治疗新选择。 03 当新机制遇见新疗法：有望成为新的基石治疗 CELMoD药物的双重作用之一即为免疫刺激特性，使其在与新型免疫疗法的联合应用中展现出理想的协同潜力。Ib期MagnetisMM-30研究[12]显示，IBER联合BCMA/CD3双特异性抗体elranatamab在包括三重耐药RRMM患者在内的群体中，确认的总缓解率（ORR）为95.5%，优于双抗单药治疗，提示了IBER与双抗的协同增效作用。随着2025 ASH年会多项CELMoD药物研究结果的公布，多发性骨髓瘤治疗正在迎来全新机制驱动的阶段性突破。这一系列临床信号表明，蕴含诺奖机制的全新靶向蛋白降解疗法CELMoD，已逐步从理论到可验证的实践转化，为未来多发性骨髓瘤治疗体系提供了一个可期待的核心支点。随着后续临床与审评进程推进，靶向蛋白降解疗法CELMoD有望成为多发性骨髓瘤治疗的新基石，为患者带来深层缓解与长期获益的新可能。参考文献： 1. Gandhi UH, Cornell RF, Lakshman A, et al. (2019) Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy. Leukemia, 33(9), 2266–2275. 2. Mateos MV, Weisel K, De Stefano V, et al. (2022) Real-world effectiveness and safety of treatments in relapsed/refractory multiple myeloma: LocoMMotion study. Haematologica, 107(9), 2174–2186. 3. Munshi NC, Anderson LD Jr, Shah N, et al. (2021) Idecabtagene vicleucel in relapsed and refractory multiple myeloma. New England Journal of Medicine, 384, 705–716. 4. Ito, T. & Handa, H. (2016) ‘Cereblon and its downstream substrates as molecular targets of immunomodulatory drugs’, International Journal of Hematology, 104: 293–299. doi:10.1007/s12185-016-2073-4. 5. Amatangelo M., et al. (2020) ‘Preclinical and translational data support development of iberdomide in combination with CD38‑ and SLAMF7‑directed monoclonal antibodies: evidence for rational combinations’, Abstract 1359, 2020 American Society of Hematology Meeting. December 5 2020. 6. Björklund C C., et al. (2020) ‘Iberdomide (CC‑220) is a potent cereblon E3 ligase modulator with antitumor and immunostimulatory activities in lenalidomide‑ and pomalidomide‑resistant multiple myeloma cells with dysregulated CRBN’, Leukemia, 34(4), pp. 1197–1201. doi:10.1038/s41375‑019‑0620‑8. 7. Aleman, A., et al. (2025). Iberdomide (IBER) treatment enhances manufactured CAR T cell expansion and functionality and is immunostimulatory in patients post-car t cell therapy. Poster PF685, EHA2025 Congress, European Hematology Association, 12–15 June 2025, Madrid, Spain 8. Jeyaraju, D., et al. Longitudinal analysis of MRD negativity and immune dynamics in patients with transplant ineligible newly diagnosed multiple myeloma treated with iberdomide, daratumumab, and dexamethasone from the CC-220-MM-001 trial. 2025 ASH Poster 2255. 9. Landgren, O., et al. A phase 2 trial of iberdomide, carfilzomib, daratumumab and dexamethasone quadruplet therapy for relapsed/refractory multiple myeloma: The ReKInDLE study. Presented at: 67th ASH Annual Meeting and Exposition in Orlando, FL. December 6, 2025. 10. Du J, Fang B, Li J, et al. A study of carfilzomib and dexamethasone in patients with relapsed and refractory multiple myeloma in China. Int J Hematol. 2021；113（3）:422-429. 11. Sureda Balari, A. et al. (2025) Iberdomide plus daratumumab and dexamethasone (IberDd) in patients with newly diagnosed multiple myeloma by renal function: A subgroup analysis of the CC-220-MM-001 trial. American Society of Hematology (ASH) Annual Meeting Abstracts, 5810. 12. Suvannasankha, A., et al. Safety and efficacy of elranatamab in combination with iberdomide in patients with relapsed or refractory multiple myeloma: Results from the phase 1b MagnetisMM-30 trial. Presented at the 2025 American Society of Hematology (ASH) Annual Meeting & Exposition; December 6, 2025.

优先审批申请上市

2026-01-26

·血液肿瘤资讯

多发性骨髓瘤“全新打法” 靶向蛋白降解剂CELMoD药物驶入快车道

整理：肿瘤资讯来源：肿瘤资讯上个月底，国家药品审评中心（CDE）官网公示，多发性骨髓瘤（MM）领域的靶向蛋白降解药物iberdomide拟被纳入优先审评程序，拟定适应症为：联合达雷妥尤单抗和地塞米松适用于治疗既往接受过至少1线治疗的多发性骨髓瘤成人患者；本月，该药物已正式获优先审评资格。图片来源：CDE官网靶向蛋白降解是近年来药物研发的热门领域，iberdomide（以下简称：IBER）所属的CELMoD平台是目前多发性骨髓瘤领域进展领先的全新靶向蛋白降解剂。CELMoD药物的作用机制借助了2004年诺贝尔化学奖解揭示的“生理性蛋白降解”功能。尽管当时业界已意识到这一生理机制的治疗潜力，但直到以CELMoD药物为代表的新型靶向蛋白降解剂问世，才真正通过理性设计，实现了对特定致病蛋白的靶向降解，为突破“不可成药”的壁垒提供了新的可能。CELMoD药物在临床层面的进展也在同步持续推进。2025美国血液学会（ASH）年会上公布的多项早期临床结果显示，CELMoD药物在不同类型的多发性骨髓瘤患者中均可观察到深度的缓解，并在联合多种疗法时表现出协同潜力，为其在多发性骨髓瘤治疗体系中的进一步探索提供了依据。众所周知，MM目前仍是不可治愈的疾病，多数患者最终会出现复发与耐药，经历反复“复发-缓解”的恶性循环，且随着治疗线数的增加，患者无进展生存期（PFS）明显缩短[1-3]。因此，延长患者在相对早线治疗阶段的控制时间，是目前MM临床决策的关键目标。这一目标的实现，核心之一在于获得更深度的缓解。也正因此，微小残留病（MRD）阴性作为目前MM最深缓解程度的疗效评价手段，在MM临床治疗中的地位日益凸显：大量研究均已证实MRD阴性与PFS等长期预后指标显著相关。而要取得更深的疾病缓解，则离不开作用机制更为精准的药物。在MM的发生发展中，多种关键致病蛋白（如Ikaros、Aiolos）是MM细胞生存和免疫调控的关键转录因子，通过传统手段难以抑制其活性，即具有“不可成药性”：如果对Ikaros/Aiolos蛋白降解的深度和特异性不足[4]，会限制整体治疗效果。靶向蛋白降解是一类利用人体自身泛素-蛋白酶体系统实现清除致病蛋白的创新机制。这一思路利用了2004年诺贝尔化学奖揭示的基础机制：泛素介导的蛋白质降解是细胞维持稳态的重要生理功能；基于此，学术界意识到，若能对该过程进行精准调节，或可为传统“不可成药”的靶点打开新的治疗通道。而CELMoD药物正是对这一机制的药物化实现。通过精准调节E3泛素连接酶复合物中负责底物识别的核心环节——CRBN，CELMoD药物可强化其底物识别能力，实现对关键致病蛋白Ikaros和Aiolos的高效、选择性降解。这种深度降解机制具备双重抗肿瘤作用：一方面可直接杀伤骨髓瘤细胞，另一方面还具有免疫刺激作用，能增强T细胞和NK细胞功能，实现更强的抗肿瘤免疫反应。从药理学层面来看，CELMoD药物的核心优势在于其可高效形成稳定的CELMoD-CRBN-靶蛋白三元复合物，以实现对Ikaros和Aiolos的强效降解。此外，CELMoD药物以单一S-异构体形式给药，可提供近100%活性成分，确保体内药效稳定，在增强疗效的同时可能降低非靶向效应带来的安全性风险。不仅如此，由于CELMoD药物具有免疫刺激的作用，使其与依赖免疫效应的现有MM疗法，如抗CD38单抗、CAR-T等，均展现出良好的协同效应[5-7]。 ASH作为血液肿瘤领域最受关注的学术会议之一，此前的2025年大会上公布了多项IBER（CELMoD药物之一）的相关临床研究，不仅展现了其实现高比例、持久MRD阴性的潜力，同时在联合新型疗法中表现出强大的协同作用，以及良好的安全性。快速、深度缓解：在广泛患者人群中实现MRD阴性随着创新疗法的不断应用，MM的治疗目标正向MRD持续阴性等更深层次的缓解迈进。2025 ASH大会上公布的两项研究显示，CELMoD药物在不同阶段MM中均展现了MRD阴性缓解方面的优势：在新诊断MM患者中，一项 IBER联合达雷妥尤单抗和地塞米松（IberDd）治疗不适合移植的新诊断多发性骨髓瘤的研究（CC-220-MM-001）[8]显示，该联合方案可诱导高比例且持久的MRD阴性缓解：高达53.3%的患者在任意时间点达到MRD阴性完全缓解（CR） [8]。而在RRMM患者中，另一项II期ReKInDLE研究[9]显示， IBER、卡非佐米、达雷妥尤单抗和地塞米松（IberKDd）四药联合方案在早线复发MM中疗效可观：在可评估患者中，62.5%的患者达到MRD阴性CR，且不良反应总体可控。以上研究提示，CELMoD药物的联合方案可诱导高比例、持久MRD阴性缓解，提示其可能改善现有药物缓解较短暂、易复发的痛点，带来更佳的长期预后。肾功能不全患者疗效不受影响，无需调整剂量肾功能不全是MM患者的常见并发症，约20%~50%的患者会在MM进程中出现肾功能不全[10]，伴肾功能不全的患者往往预后更差，临床治疗面临挑战。CC-220-MM-001研究亚组分析[11]显示，接受IberDd方案治疗的患者，无论肾损伤程度如何，其疗效（ORR、≥CR）和安全性均无显著差异，且肾损伤状态不影响IBER的清除率。这一发现提示轻、中度肾功能损伤患者无需调整IBER的剂量，有望为该类特殊人群的治疗带来有效、安全性良好的治疗新选择。联合治疗，协同增效：拓展新型疗法应用前景 CELMoD药物的双重作用之一即为免疫刺激特性，使其在与新型免疫疗法的联合应用中展现出理想的协同潜力。Ib期MagnetisMM-30研究 [12]显示，IBER联合BCMA/CD3双特异性抗体elranatamab在包括三重耐药RRMM患者在内的群体中，确认的总缓解率（ORR）为95.5%，提示了IBER与双抗的协同增效作用。随着2025 ASH年会多项CELMoD药物研究结果的公布，多发性骨髓瘤治疗正在迎来全新机制驱动的阶段性突破。这一系列临床信号表明，蕴含诺奖机制的全新靶向蛋白降解疗法CELMoD，已逐步从理论到可验证的实践转化，为未来多发性骨髓瘤治疗体系提供了一个可期待的核心支点。随着后续临床与审评进程推进，靶向蛋白降解疗法CELMoD有望成为多发性骨髓瘤治疗的新基石，为患者带来深层缓解与长期获益的新可能。参考文献 1.Gandhi UH, Cornell RF, Lakshman A, et al. (2019) Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy. Leukemia, 33(9), 2266–2275.2.Mateos MV, Weisel K, De Stefano V, et al. (2022) Real-world effectiveness and safety of treatments in relapsed/refractory multiple myeloma: LocoMMotion study. Haematologica, 107(9), 2174–2186.3.Munshi NC, Anderson LD Jr, Shah N, et al. (2021) Idecabtagene vicleucel in relapsed and refractory multiple myeloma. New England Journal of Medicine, 384, 705–716.4.Ito, T. & Handa, H. (2016) ‘Cereblon and its downstream substrates as molecular targets of immunomodulatory drugs’, International Journal of Hematology, 104: 293–299. doi:10.1007/s12185-016-2073-4.5.Amatangelo M., et al. (2020) ‘Preclinical and translational data support development of iberdomide in combination with CD38‑ and SLAMF7‑directed monoclonal antibodies: evidence for rational combinations’, Abstract 1359, 2020 American Society of Hematology Meeting. December 5 2020.6.Björklund C C., et al. (2020) ‘Iberdomide (CC‑220) is a potent cereblon E3 ligase modulator with antitumor and immunostimulatory activities in lenalidomide‑ and pomalidomide‑resistant multiple myeloma cells with dysregulated CRBN’, Leukemia, 34(4), pp. 1197–1201. doi:10.1038/s41375‑019‑0620‑8.7.Aleman, A., et al. (2025). Iberdomide (IBER) treatment enhances manufactured CAR T cell expansion and functionality and is immunostimulatory in patients post-car t cell therapy. Poster PF685, EHA2025 Congress, European Hematology Association, 12–15 June 2025, Madrid, Spain8.Jeyaraju, D., et al. Longitudinal analysis of MRD negativity and immune dynamics in patients with transplant ineligible newly diagnosed multiple myeloma treated with iberdomide, daratumumab, and dexamethasone from the CC-220-MM-001 trial. 2025 ASH Poster 2255.9.Landgren, O., et al. A phase 2 trial of iberdomide, carfilzomib, daratumumab and dexamethasone quadruplet therapy for relapsed/refractory multiple myeloma: The ReKInDLE study. Presented at: 67th ASH Annual Meeting and Exposition in Orlando, FL. December 6, 2025.10.Du J, Fang B, Li J, et al. A study of carfilzomib and dexamethasone in patients with relapsed and refractory multiple myeloma in China. Int J Hematol. 2021；113（3）:422-429.11.Sureda Balari, A. et al. (2025) Iberdomide plus daratumumab and dexamethasone (IberDd) in patients with newly diagnosed multiple myeloma by renal function: A subgroup analysis of the CC-220-MM-001 trial. American Society of Hematology (ASH) Annual Meeting Abstracts, 5810.12.Suvannasankha, A., et al. Safety and efficacy of elranatamab in combination with iberdomide in patients with relapsed or refractory multiple myeloma: Results from the phase 1b MagnetisMM-30 trial. Presented at the 2025 American Society of Hematology (ASH) Annual Meeting & Exposition; December 6, 2025. 责任编辑：elva 排版编辑：Niko

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100 项与伊伯多胺相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
多发性骨髓瘤	申请上市	中国	Bristol-Myers Squibb Pharma EEIG	2025-12-29
多发性骨髓瘤	申请上市	中国	Celgene International SARL	2025-12-29
难治性多发性骨髓瘤	临床2期	美国	Bristol Myers Squibb Co.	2024-02-20
阴燃多发性骨髓瘤	临床2期	美国	Bristol Myers Squibb Co.	2021-11-02
侵袭性 B 细胞非霍奇金淋巴瘤	临床2期	美国	Celgene Corp.	2021-10-10
侵袭性 B 细胞非霍奇金淋巴瘤	临床2期	奥地利	Celgene Corp.	2021-10-10
侵袭性 B 细胞非霍奇金淋巴瘤	临床2期	比利时	Celgene Corp.	2021-10-10
侵袭性 B 细胞非霍奇金淋巴瘤	临床2期	法国	Celgene Corp.	2021-10-10
侵袭性 B 细胞非霍奇金淋巴瘤	临床2期	韩国	Celgene Corp.	2021-10-10
侵袭性 B 细胞非霍奇金淋巴瘤	临床2期	西班牙	Celgene Corp.	2021-10-10

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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


NCT04392037 (ICON, Pubmed \| Lancet Haematol)	临床2期	复发性多发性骨髓瘤	61	dexamethasonecyclophosphamideIberdomide + dexamethasonecyclophosphamideIberdomidehamide + dexamethasonecyclophosphamideIberdomideone (relapsed and refractory multiple myeloma)	獵遞製齋鹽憲醖夢獵鏇(範襯鹹鹹膚鹹願膚蓋鬱) = 34% of patients experienced infections 餘積鹹範窪鬱獵蓋鑰糧 (範積壓鏇鹽襯夢壓範齋 ) 更多	积极	2026-01-01
NCT05354557 (ASH2025)	临床2期	维持	15	Iberdomide 1 mg	壓壓鏇選構繭構餘鹽憲(夢餘選艱繭廠艱糧築鑰) = 鑰製製鑰淵艱膚憲獵願積鏇鏇膚願構範鏇觸鏇 (積衊膚積憲餘範鹹築醖 ) 更多	积极	2025-12-06
NCT04564703 (EMN26, ASH2025)	临床2期	多发性骨髓瘤维持	120	Iberdomide 0.75 mg	獵顧鬱獵範繭網淵鑰鏇(憲繭製鹹鹽網鏇簾願夢) = neutropenia (48% in the 0.75 mg, 58% in the 1.0 mg, and 60% in the 1.3 mg cohorts), followed by infections (8%, 18%, and 18%; mostly respiratory infections). Grade ≥3 rash was more frequent in the 1.3 mg cohort (10%), compared to 0.75 mg (0%) and 1.0 mg (3%) cohorts. There were no grade ≥3 AEs of thrombocytopenia, anemia, or venous thromboembolism. Only 1 of 120 pts (0.8%) developed grade ≥3 neuropathy (1.3 mg), and 1 (0.8%) developed grade 3 diarrhea (1.0 mg). 淵鏇廠夢夢觸顧鑰繭獵 (鬱醖艱壓積觸壓簾醖築 )	积极	2025-12-06
NCT04564703 (EMN26, ASH2025)	临床2期	多发性骨髓瘤维持	120	Iberdomide 1.0 mg		积极	2025-12-06
NCT05896228 (ReKInDLE, ASH2025)	临床2期	复发性多发性骨髓瘤	30	Iberdomide+Carfilzomib+Daratumumab+Dexamethasone	願築積艱鹹顧願蓋選鬱(憲憲鑰夢窪繭鹹廠鏇蓋) = Grade 3 or greater events included neutropenia (50%), lymphocytopenia (40%), leukopenia (23%), thrombocytopenia (10%), and anemia (3%) but were manageable with growth factor support and/or iber dose-reduction, as needed. 製獵壓夢鹹齋壓鑰選齋 (繭願衊鑰壓遞獵構積壓 ) 更多	积极	2025-12-06
ACTRN12621001037897 (IBIS, ASH2025)	临床1期	多发性骨髓瘤	29	Iberdomide+Isatuximab+Dexamethasone	鏇齋製簾齋遞選築夢廠(簾壓齋遞鏇構壓顧襯鏇) = 蓋衊選襯襯鬱衊獵築夢鬱繭醖憲蓋繭網廠廠廠 (憲遞淵積鏇鬱範蓋範夢, 50.3 ~ 82.6) 更多	积极	2025-12-06
ALLG MM25 (ASH2025)	临床1/2期	多发性骨髓瘤 t(11;14)	20	Venetoclax+Iberdomide+dexamethasone	鑰獵壓夢鹹簾觸醖觸衊(遞顧醖簾鏇築衊齋顧醖) = 鑰繭繭糧鬱齋艱膚觸遞鹽鹹憲範觸築糧餘獵鹽 (選獵醖鏇醖願簾繭製艱 ) 更多	积极	2025-12-06
NCT02773030 (CC-220-MM-001, ASH2025)	临床1/2期	多发性骨髓瘤	75	Iberdomide plus daratumumab and dexamethasone (IberDd)	衊範鹹構鹽鑰鹹餘鬱醖(夢鏇鬱鏇糧衊鬱鹹範壓) = 糧築糧壓蓋鏇鹹簾鬱範廠鏇觸餘顧襯顧構淵艱 (網餘襯鹹壓糧簾糧鏇構 ) 更多	积极	2025-12-06
NCT02773030 (CC-220-MM-001, ASH2025)	临床1/2期	多发性骨髓瘤	75	Iberdomide plus daratumumab and dexamethasone (IberDd) (No renal impairment)	衊範鹹構鹽鑰鹹餘鬱醖(夢鏇鬱鏇糧衊鬱鹹範壓) = 獵醖蓋網壓廠獵艱積遞廠鏇觸餘顧襯顧構淵艱 (網餘襯鹹壓糧簾糧鏇構 ) 更多	积极	2025-12-06
NCT04975997 (EXCALIBER-RRMM, Company_Website) 人工标引	临床3期	多发性骨髓瘤	664	Dexamethasone+Iberdomide+Daratumumab	糧鹹鹽醖觸糧鹹衊鹽鬱(鹽窪選夢夢鑰鹹餘鹹範) = demonstrated a statistically significant improvement 製壓選蓋構蓋鑰繭遞夢 (鑰艱獵顧繭夢淵醖窪鏇 )	积极	2025-09-23
NCT04975997 (EXCALIBER-RRMM, Company_Website) 人工标引	临床3期	多发性骨髓瘤	664	Dexamethasone+Daratumumab+Bortezomib		积极	2025-09-23
NCT05199311 (phase 1/2 study, ASCO2025)	临床2期	多发性骨髓瘤	38	Carfilzomib, iberdomide, and dexamethasone (KID)	鏇簾糧蓋構範憲餘鏇鏇(艱廠觸淵齋齋願艱選網) = 製積觸鬱鏇膚鑰網憲製鹹鹽膚膚鹽衊鹹鬱鏇鏇 (繭襯簾壓窪鏇網醖網鬱 ) 更多	积极	2025-05-30
NCT02773030 (CC-220-MM-001, ASCO2025)	临床1/2期	多发性骨髓瘤	18	Iberdomide, bortezomib, and dexamethasone (IberVd)	夢鹽遞膚構齋壓鹽鏇網(遞蓋蓋艱廠選簾鏇鏇壓) = 14 (82.4%) pts had grade (Gr) 3/4 treatment-emergent AEs (TEAEs); primarily infections (47.1%), including pneumonia (17.6%) and COVID-19 (11.8%) 鏇構製構遞憲簾觸廠艱 (製構淵餘襯膚憲憲觸蓋 ) 更多	积极	2025-05-30