Inobrodib

ASH Annual Meeting and Exposition leaves the oncology community buzzing over a series of late-breaking presentations that experts are calling 'unprecedented.' Major pharmaceutical developers such as Johnson & Johnson, Arcellx, Gilead, Bristol Myers Squibb, Regeneron, AbbVie, CellCentric, Adaptive Biotechnologies, and others, presented pivotal data across the multiple myeloma treatment landscape, with results suggesting that long-term disease-free survival—and potentially a 'functional cure'—is becoming a reality for more patients. LAS VEGAS, Dec. 11, 2025 /PRNewswire/ -- The 67th American Society of Hematology (ASH) Annual Meeting, held December 6-9, 2025, in Orlando, Florida, showcased groundbreaking clinical advances in multiple myeloma treatment from leading biopharmaceutical companies. The conference featured unprecedented efficacy data demonstrating potential functional cures and innovative approaches across novel immunotherapies, bispecific antibodies, and next-generation targeted agents, signaling a major shift in how the disease is managed. Download the updated multiple myeloma market report featuring key results from ASH 2025 @ Multiple Myeloma Market Let's dive deep into the promising results presented at the ASH conference 2025 Johnson & Johnson's TECVAYLI Plus DARZALEX: Setting New Standard of Care Johnson & Johnson unveiled late-breaking results from the Phase III MajesTEC-3 study, presenting what has been characterized as the most impressive progression-free survival (PFS) benefit ever demonstrated in a Phase III multiple myeloma trial. The study evaluated the combination of TECVAYLI (teclistamab-cqyv), a first-in-class BCMAxCD3 bispecific antibody, combined with DARZALEX FASPRO (daratumumab plus hyaluronidase-fihj), a subcutaneous anti-CD38 monoclonal antibody. The combination demonstrated a hazard ratio of 0.17 for PFS—described as "the best hazard ratio we've seen in a phase III clinical trial in multiple myeloma" by lead investigator María-Victoria Mateos, MD, PhD, from the University of Salamanca. At three years of follow-up, 83.4% of patients treated with the teclistamab-dara combination remained alive and progression-free compared to just 29.7% in the control arm, with a median PFS not yet reached in the treatment group versus 18.1 months in controls. Beyond PFS, the data demonstrated sustained benefits across secondary endpoints. Complete response rates of 81.8% were achieved with the combination, compared to 31% in the control group, while minimal residual disease (MRD)-negative rates reached 57.6%, compared to 3.4% in controls. Overall survival was significantly prolonged, with a hazard ratio of 0.45; 91% of patients who were progression-free at six months remained progression-free at three years, suggesting a potential "functional cure" for relapsed/refractory multiple myeloma patients. Safety remained manageable despite the combination's potency. Cytokine release syndrome occurred in approximately 60% of patients. Still, it was limited to Grade 1 or 2 severity in all cases, while immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in only 1.1% of patients, all of which resolved. Deaths were approximately 50% lower with the combination compared to controls (15.9% versus 33.1%), with minimal treatment discontinuations due to adverse events (4.6% versus 5.5%). Gilead/Legend Biotech's CARVYKTI: Extended Follow-Up Affirms CAR-T Durability Gilead and Legend Biotech presented extended durability data for CARVYKTI (ciltacabtagene autoleucel), a BCMA-directed CAR T-cell therapy, demonstrating sustained disease control in patients with multiple myeloma. New Phase 3 data revealed that 80.5% of patients had not experienced disease progression at 30 months of follow-up, with 87.3% remaining alive after 2.5 years. The enduring response rates substantially exceed historical outcomes in heavily pretreated patient populations. In earlier trials evaluating cilta-cel after three or more prior lines of therapy, progression-free survival reached 59.9% with an overall survival of 70.6%, underscoring the durability advantage of this single-infusion therapy. The approval of CARVYKTI as a first relapse option represents a significant advancement, allowing earlier intervention in the disease course for appropriate patients. Bristol Myers Squibb's Iberdomide: Deepening Response Depth in Newly Diagnosed Myeloma Bristol Myers Squibb revealed compelling data on iberdomide, an oral cereblon E3 ligase modulator (CELMoD) agent, demonstrating that the drug delivers deep and sustained responses in newly diagnosed multiple myeloma. A Phase 2 clinical trial examining different doses of iberdomide as maintenance therapy following autologous stem-cell transplantation enrolled 120 patients and showed that approximately half achieved MRD negativity (no detectable cancer), with over 80% remaining cancer-free after two years. Additional Phase 1b/2a data supported the efficacy and safety of iberdomide in combination with daratumumab and dexamethasone for transplant-deferred or ineligible newly diagnosed patients, demonstrating robust responses with sustained minimal residual disease (MRD) negativity. A cooperative group analysis of iberdomide maintenance after autologous stem-cell transplantation continued to show benefit, positioning this agent as a valuable maintenance option across multiple treatment settings. Furthermore, BMS presented Phase 1b data on elranatamab combined with iberdomide ( MagnetisMM-30 trial) in relapsed/refractory multiple myeloma patients, achieving a 95.5% objective response rate with a safety profile consistent with known toxicities of each agent. Regeneron's LYNOZYFIC: First BCMA×CD3 Bispecific in Frontline Setting Regeneron showcased data on LYNOZYFIC (linvoseltamab-gcpt), a bispecific antibody targeting BCMA and CD3, highlighting promising early clinical results as a monotherapy for newly diagnosed multiple myeloma patients. The Phase 1/2 LINKER MM4 trial represents the first evaluation of a BCMA×CD3 bispecific antibody as monotherapy in the frontline myeloma setting, potentially redefining initial treatment strategies. Updated results from the LINKER MM2 study, in which LYNOZYFIC was combined with different anti-CD38 monoclonal antibodies in relapsed or refractory patients, further demonstrated the drug's potential to redefine treatment approaches at early disease stages and improve patient outcomes. Regeneron's hematology program demonstrated significant momentum with regulatory approvals for blood cancer treatments throughout 2025. AbbVie's Etentamig: Next-Generation T-Cell Engager Shows Promise AbbVie presented Phase 1b data evaluating etentamig, a BCMAxCD3 bispecific T-cell engager, in combination with pomalidomide and dexamethasone in 85 heavily pretreated relapsed/refractory multiple myeloma patients who had received at least three prior lines of therapy. The combination demonstrated the therapeutic potential of AbbVie's T-cell engager approach in this difficult-to-treat patient population. CellCentric's Inobrodib: Novel Oral Mechanism for Treatment-Resistant Patients CellCentric unveiled Phase 2 dose optimization results for inobrodib in combination with pomalidomide plus dexamethasone, demonstrating strong clinical efficacy in heavily pretreated relapsed/refractory multiple myeloma patients. Among heavily pretreated patients (median five prior lines of therapy) who were pomalidomide-refractory and had previously failed on BCMA and/or T-cell engager therapy, inobrodib achieved objective response rates of 60% at 20 mg and 75% at 30 mg—representing at least a two-fold increase compared to real-world response rates of 25-30% in similar patient populations after BCMA/bispecific agents. As an oral small-molecule drug targeting p300/CBP bromodomains, inobrodib offers a differentiated mechanism of action for patients ineligible for, or after, bispecific and BCMA-targeting agents. The favorable tolerability profile, with the most common adverse events being cytopenias and fatigue, positions this agent as a compelling option for community-based treatment, where more than 70% of myeloma patients are managed. Arcellx's Anitocabtagene Autoleucel: Novel CAR-T Architecture Arcellx presented new clinical data from the iMMagine-1 study evaluating anitocabtagene autoleucel (anito-cel), the first BCMA CAR T-cell therapy utilizing the company's novel compact D-Domain technology, in patients with relapsed or refractory multiple myeloma. This differentiated CAR-T architecture represents an innovative approach to autologous T-cell immunotherapy in multiple myeloma. Adaptive Biotechnologies' clonoSEQ: MRD Testing Drives Treatment Decisions Adaptive Biotechnologies showcased the expanding clinical utility of clonoSEQ, a minimal residual disease (MRD) detection test, with 32 abstracts focused on multiple myeloma at ASH 2025. Presentations highlighted the growing use of clonoSEQ to evaluate treatment response, real-world evidence linking MRD status to clinical outcomes, and guidance on treatment strategies. Notably, Phase 2 AURA trial data involving 200 newly diagnosed multiple myeloma patients demonstrated that profound MRD responses and sustained MRD negativity were associated with significantly enhanced progression-free survival. The test's critical role in identifying optimal candidates for intensified maintenance therapy in MRD-positive patients post-transplant was particularly emphasized, with data showing substantially higher MRD-negativity rates when guided by clonoSEQ. Live MMR Vaccine Safety in Daratumumab-Treated Myeloma Patients New research presented at ASH 2025 addressed an important question regarding vaccine safety in multiple myeloma patients receiving immunosuppressive therapy. A clinical trial of 41 patients with multiple myeloma who had undergone autologous stem-cell transplantation and were receiving daratumumab demonstrated that the live MMR vaccine was safe and well-tolerated in this population. None of the vaccinated patients developed active measles, mumps, or rubella disease following vaccination, with no hospitalizations or deaths reported. Multiple Myeloma Market Implications and Expansion The convergence of unprecedented efficacy data across multiple modalities has profound implications for the multiple myeloma market. The multiple myeloma therapeutic market, estimated at $22 billion in 2024, is projected to grow at a significant CAGR, reaching $33 billion by 2034, growth substantially accelerated by these clinical advances. The rapid advancement of bispecific antibodies, CAR-T therapies, and next-generation proteasome inhibitors has expanded treatment options but intensified competitive pressures. For Johnson & Johnson, overlap between TECVAYLI-based combination regimens and its approved CAR-T product, CARVYKTI, raises a risk of internal market cannibalization, potentially driving the company to accelerate the rollout of combination strategies to protect its commercial footing. Meanwhile, Bristol Myers Squibb, the Genmab/Pfizer alliance, and newer entrants are shaping a market trajectory in which bispecific and CAR-T platforms increasingly dominate the relapsed/refractory landscape. Still, proteasome inhibitors continue to command a significant share in frontline and maintenance settings. In summary, the 2025 ASH Annual Meeting marks a pivotal moment for multiple myeloma treatment. Data showing that bispecific combinations, CAR-T therapies, and other emerging modalities can deliver deep, durable responses, with the possibility of functional cures for some patients, redefines expectations for a disease long viewed as incurable. The combination of unprecedented efficacy, better safety, and improved accessibility driven by manufacturing advances positions the multiple myeloma market for significant growth. Source: Multiple Myeloma Market Report Multiple Myeloma Market Insights, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key multiple myeloma companies, including Sanofi, Karyopharm Therapeutics, Takeda Pharmaceutical, Celgene, Bristol-Myers Squibb, RAPA Therapeutics, Pfizer, Array Biopharma, Cellectar Biosciences, BioLineRx, Celgene, Aduro Biotech, ExCellThera, Janssen Pharmaceutical, Precision BioSciences, Takeda, Glenmark (Ichnos Sciences SA), Poseida Therapeutics, Molecular Partners AG, Chipscreen Biosciences, AbbVie, Genentech (Roche), Janssen Biotech, Nanjing Legend Biotech, Merck Sharp & Dohme Corp., among others. 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吉西他滨耐药性仍是胰导管腺癌（PDAC）患者生存率低的主要决定因素，凸显了迫切需要阐明其分子机制并开发有效对策。2025年11月27日，中山大学殷晓煜唯一通讯在Advanced Science（IF=14.1）在线发表题为“Positive Feedback Loop of Histone Lactylation-Driven HNRNPC Promotes Autophagy to Confer Pancreatic Ductal Adenocarcinoma Gemcitabine Resistance”的研究论文。研究建立了耐药吉西他滨胰腺癌细胞系和患者源性异种移植（PDX）模型，随后进行高通量测序，鉴定出异质核核糖核蛋白C（HNRNPC）作为化疗耐药肿瘤中显著上调的因子。 HNRNPC表达的沉默能显著恢复体外和体内对吉西他滨治疗的敏感性。机制上，多组学分析显示组蛋白H3赖氨酸18乳酸化（H3K18la）驱动HNRNPC过表达。HNRNPC以N6-甲基腺苷（m6A）依赖性方式稳定TNF受体相关因子6（TRAF6）转录本，从而激活自噬以介导吉西他滨耐药性。同时，HNRNPC通过类似方式稳定乙醛脱氢酶1家族成员A3（ALDH1A3）mRNA，调控代谢重编程级联反应，增强糖酵解水平和H3K18la修饰水平，形成组蛋白乳酸化-HNRNPC正反馈环路。值得注意的是，使用673A（一种ALDH1A3药理学抑制剂）可有效破坏该调控环路，并与吉西他滨在PDX模型中产生协同治疗效果。这些发现不仅揭示了组蛋白乳酸化驱动的正反馈环路通过HNRNPC介导的自噬激活维持化疗耐药的分子机制，还证实673A有望成为克服PDAC吉西他滨耐药的潜在临床候选药物。 另外，2024年11月3日，中山大学殷晓煜、许琼聪共同通讯在Advanced Science  在线发表题为“Epigenetic Activation of the CMTM6-IGF2BP1-EP300 Positive Feedback Loop Drives Gemcitabine Resistance in Pancreatic Ductal Adenocarcinoma”的研究论文。该研究为了揭示吉西他滨耐药的潜在机制，建立了吉西他滨耐药的PDAC细胞系和患者来源的异种移植(PDX)模型并进行RNA测序。结果发现，CMTM6与PDAC中的吉西他滨耐药密切相关。多组学分析显示，EP300介导的H3K27ac修饰参与了CMTM6的转录激活，通过阻止其泛素化来维持IGF2BP1的表达。m6A读取器IGF2BP1通过识别m6A修饰来稳定EP300和MYC mRNA，形成正反馈回路，增强肿瘤干性并最终导致PDAC耐药性。EP300抑制剂inobrodib与吉西他滨联合使用对PDAC具有协同作用。总体而言，这些发现表明EP300–CMTM6–IGF2BP1正反馈回路通过表观遗传重编程促进吉西他滨耐药性，而inobrodib与吉西他滨联合使用代表了一种克服PDAC化学耐药性的有希望的策略，值得在临床试验中进一步研究。 胰管腺癌（PDAC）是肿瘤学中最致命的恶性肿瘤之一，其特征是预后极差。约80%的患者在确诊时已出现局部进展或远处转移，导致大多数病例无法进行手术干预，进一步加剧了临床治疗的复杂性⁠。目前，晚期PDAC的治疗方案仍以吉西他滨为基础的联合化疗作为全身治疗的核心⁠。尽管部分患者对吉西他滨治疗初始表现出临床应答，但化疗耐药性的快速出现始终限制着治疗获益，显著影响治疗结局⁠。这些临床挑战凸显了开发增强吉西他滨化疗敏感性的创新策略、阐明治疗耐药潜在分子机制的迫切需求，进而寻找新的治疗靶点以改善PDAC患者的临床预后。N6-甲基腺苷（m6A）是真核生物中最普遍的mRNA内部修饰，作为关键的表观遗传机制调控转录后基因表达⁠。这种动态修饰通过“写入酶”复合物（甲基转移酶）与“擦除酶”蛋白（去甲基化酶）的拮抗作用实现精准调控平衡。m6A修饰的生物学效应由特异性“读取蛋白”执行，这些蛋白通过选择性结合解码甲基化模式，进而对RNA代谢进行时空调控⁠。新兴证据表明，m6A甲基化在各种恶性肿瘤的发生和进展中起着关键调控作用。异质核核糖核蛋白C（HNRNPC）是异质核核糖核蛋白（hnRNPs）的一个亚家族，通过与mRNA结合，参与RNA的切割调控、mRNA稳定和核细胞质运输机制，功能上参与RNA代谢过程。积累的证据显示HNRNPC在多种人类癌症中扮演关键角色。 近期的研究中，发现吉西他滨耐药的PDAC中HNRNPC表达上调，因此推测HNRNPC可能在PDAC吉西他滨耐药中发挥关键作用。组蛋白乳酸化作为一种新发现的翻译后修饰，已被证实可调控基因表达。该修饰主要发生在赖氨酸残基上，尤其以组蛋白H3 赖氨酸18（H3K18la）为主要位点⁠。越来越多的证据表明，H3K18la通过转录调控在多种恶性肿瘤中发挥重要作用。然而，组蛋白乳酸化在PDAC 吉西他滨耐药中的作用仍有待阐明。 药物673A通过靶向该反馈信号增强吉西他滨对吉西他滨耐药PDAC的治疗效果。图自：Advanced Science 基于这些发现，本研究旨在阐明HNRNPC是否对PDAC中的吉西他滨耐药性有贡献。分析结果显示，HNRNPC在吉西他滨耐药PDAC细胞、患者来源异种移植（PDX）模型及临床标本中均持续上调，且其高表达与吉西他滨治疗应答不佳显著相关。机制上，研究发现H3K18la可转录激活HNRNPC表达。体外和体内功能研究均证实，沉默HNRNPC可显著恢复吉西他滨耐药PDAC对吉西他滨的敏感性。作为m6A“读取蛋白”，HNRNPC通过识别m6A修饰稳定肿瘤坏死因子受体相关因子6（TRAF6）mRNA，进而导致TRAF6介导的自噬激活，最终引发PDAC吉西他滨耐药。 此外，HNRNPC通过类似的m6A依赖机制同时稳定乙醛脱氢酶1家族成员A3（ALDH1A3）mRNA，通过激活糖酵解通路驱动代谢重编程。这种代谢转变通过增加乳酸生成及后续组蛋白乳酸化形成正反馈环路，进一步放大HNRNPC表达。值得注意的是，在PDX模型中，ALDH1A3治疗性抑制与吉西他滨联合使用可协同抑制PDAC增殖，凸显了该靶向策略的应用潜力。 来源：iNature 原文链接： https://doi.org/10.1002/advs.202510483 往期基因编辑·CNS快讯相关推文 复旦大学杨玲/左伋/张群岭发现介导外周 T 细胞淋巴瘤的化疗耐药性的调控新机制 南京大学魏嘉/李颜合作揭示了MHC-II限制性新抗原疫苗逆转免疫抵抗新机制 复旦大学沈坤堂等发现癌症相关成纤维细胞通过PGK1介导的代谢重编程促进胃肠道间质肿瘤对伊马替尼的耐药性 浙江大学王晓健/林文龙等发现自身免疫性疾病治疗的潜在新靶点 华中科技大学向明团队发现1型糖尿病发病过程的调控新机制 威斯腾生物基因编辑·前沿热点服务项目 基因编辑|铁死亡|肿瘤代谢|肿瘤免疫|细胞自噬 外泌体|细胞焦亡|类器官|单细胞测序|单细胞代谢   病理空间组|脑科学|circRNA|lncRNA|相分离 线粒体|干细胞|组蛋白|肠道菌群|免疫调控 转录调控|内质网|高内涵筛药 更多科研请咨询：400-675-6758 凡来电咨询者皆可免费领取一张基因编辑敲除细胞2000元代金券 威斯腾生物成立于2007年，是一家聚焦基因功能研究与肿瘤早期诊断产品开发领域的生物高科技公司；是国家高新技术企业、科技型企业、中关村生物医药研发检测共享平台，18年专注模式动物构建、多病毒包装改造、多组学研究、基因编辑研究、基因调控、基因靶点发现验证等高质量基因功能研究CRO平台。 威斯腾生物放眼于全球生命科学基因功能研究前沿技术创新转化应用开发，立足于全国生命科学基因功能研究高品质技术服务，以肿瘤早诊、快诊以及传染病快速诊断为创新转化方向；以CRISPR/Cas9-13a基因编辑、类器官研究、外泌体研究、空间病理组学、基因及蛋白互作、CtDNA超微量捕获为核心特色技术。 威斯腾生物研发团队由华人科学家Jiang Guo教授领衔，2位海外院士、5位千人专家、2位长江学者、2位全国科技领军人才共同组建，北美研发中心设在美国·纽约州，中国研发中心分别位于北京大兴、重庆高新区和上海浦东区，在全国22个省市建立了直属运营中心。 威斯腾生物以赋能“生命科学基因功能研究”为己任，加快肿瘤早诊创新产品开发进程，推动生命科学基因功能研究行业发展，为人类健康保驾护航。 威斯腾生物·生命科学部·服务项目 细胞生物学 | 分子生物学  多组学研究 | 表观遗传学研究 机制/通路研究 | 基因功能研究 动物建模 | CRISPR/Cas9基因编辑 更多科研请咨询：400-675-6758 凡来电咨询者皆可免费领取一份高纯度质粒提取试剂盒，包邮到家！ 诚聘编辑（兼职/在线办公） 脑科学研究 | 基因编辑 | 类器官 | 基因调控 肿瘤微环境 | miRNA研究 | 流式应用 脂代谢组 | 蛋白组学 | 蛋白质互作 免疫 | 干细胞 …… 【详情咨询】 QQ：3636762840 电话：400-675-6758 版权声明：除原创内容及特别说明之外，推送稿件部分文字及图片均来自网络及主流媒体。如认为有侵权内容，请联系我们删除。 End