Vinblastine Sulfate

在过去十年中，抗体药物偶联物（ADCs）的发展为提高细胞毒性药物的疗效和降低毒性带来了希望，与传统细胞毒性化疗药物相比具有显著临床优势。ADCs将单克隆抗体的精准靶向性、特异性和细胞毒性化疗药物的强大杀伤力相结合，其核心理念是通过最小化系统毒性来拓宽药物的治疗指数。一般来说，ADC的结构组成包括一个靶向肿瘤特异性抗原或相关抗原的抗体，以及通过连接子连接到抗体上的多个细胞毒性分子（也称为载荷）。当ADC进入血液循环后，它会选择性地结合到肿瘤细胞表面表达的受体上。随后，受体-ADC复合物通过内吞作用被内化。在肿瘤中，连接子被切割，细胞毒性载荷被释放，游离的载荷通过其作用机制诱导细胞死亡。很多人认为，ADC设计的关键因素主要集中在抗体的选择上，因为抗体是将细胞毒性药物递送至肿瘤的载体。有趣的是，尽管抗体的选择很重要，但ADC的连接子稳定性以及载荷的选择可能对临床成功更为关键。一个很好的例子是用于治疗HER2阳性转移性乳腺癌的两种ADC药物：德曲妥珠单抗（ENHERTU）和恩美曲妥珠单抗（KADCYLA）。在一项三期研究中，研究者比较了德曲妥珠单抗与恩美曲妥珠单抗在既往接受过曲妥珠单抗和紫杉类治疗的HER2阳性转移性乳腺癌患者中的疗效，主要终点是无进展生存期。尽管两种ADC药物使用了相同的抗体，但接受德曲妥珠单抗治疗的患者疾病进展或死亡的风险显著低于接受恩美曲妥珠单抗治疗的患者。在524名随机分配的患者中，12个月时无疾病进展且存活的患者比例在德曲妥珠单抗组为75.8%，而在恩美曲妥珠单抗组为34.1%。两种ADC采用的同一抗体，差异主要在连接子和载荷方面（如下表示例所示）。这些结果突显了在ADC开发早期阶段选择最合适的载荷分子（以及连接子设计）的重要性。这一理念在当前ADC竞争激烈的环境中尤为重要。许多ADC药物在临床开发过程中因毒性过大而失败，包括血液学、肝脏、神经学和眼部事件等，这些毒性削弱了药物的获益-风险比。实际上，许多已获批的ADC药物仍有一定比例的患者因ADC相关毒性需要减少剂量、暂停治疗或停止治疗。本文围绕ADC设计中细胞毒性载荷发现和开发的关键属性和考量因素展开。常见载荷ADC本质上是通过携带的载荷杀伤癌细胞，载荷的选择就显得尤为重要。在ADC药物发展的早期阶段，载荷以传统的化疗药物如甲氨蝶呤、长春碱和阿霉素等细胞毒性药物为主。然而，由于这类ADC药物对癌细胞的细胞毒性效力不足以及在肿瘤细胞内的蓄积量低，导致疗效一般，临床试验陆续失败。研究显示，经静脉给药后，只有大约1%到2%的ADC分子能够到达目标肿瘤部位。这就要求载荷需要具有很高的活性（IC50值处于低纳摩尔和皮摩尔水平）。目前，已获批ADC药物的载荷主要有两大类高活细胞毒性药物：抗微管药物（例如奥瑞他汀类和美登素类）以及造成DNA损伤的药物（例如喜树碱类、卡利霉素类和吡咯并苯二氮䓬类）微管蛋白抑制剂微管是细胞骨架的主要组成部分，在细胞分裂过程中发挥着关键作用，尤其是在肿瘤细胞快速增殖期间。微管蛋白抑制剂可分为两类：微管聚合促进剂和微管聚合抑制剂。这两类分子均是通过干扰微管依赖的有丝分裂发挥作用。奥瑞他汀（Auristatin）是一种合成的抗肿瘤药物，源自天然产物dolastatin 10。Dolastatin 10本身是一种非特异性毒性药物，因此不被用作ADC载荷。然而，其结构类似物如单甲基奥瑞他汀E（MMAE）通过阻断微管聚合过程，导致细胞周期停滞，已在ADC中大量使用。例如，已上市ADC产品Adcetris的细胞毒性载荷就是MMAE，用于治疗复发或难治性霍奇金淋巴瘤和系统性间变性大细胞淋巴瘤。美登素类（Maytansinoids）通过阻止微管二聚体聚合形成成熟微管来抑制有丝分裂和细胞复制。美登素类是从灌木Maytenus serrata中分离出来的天然产物，目前有两种美登素衍生物DM1和DM4被用于ADC设计。其中，DM1是用于治疗HER2扩增型乳腺癌的ADC药物Kadcyla的弹头。DNA损伤剂顾名思义，DNA损伤剂是一类能够对DNA分子造成损伤的化合物，通过干扰DNA的正常结构和功能，从而抑制细胞增殖、诱导细胞周期停滞或细胞凋亡。严格意义上讲，虽然微管破坏剂主要通过干扰微管蛋白的聚合来抑制细胞分裂，但它们也可以间接导致DNA损伤，算是DNA损伤剂的一种。除此以外，还有两类主要的DNA损伤剂：一类是拓扑异构酶I抑制剂（Topoisomerase I Inhibitors），通过干扰DNA的拓扑结构，阻止DNA复制和转录，从而诱导细胞凋亡。目前，大多数拓扑异构酶I抑制剂是喜树碱（camptothecin）的衍生物，包括拓扑替康（Topotecan）、司他曲安（Govitecan）、SN-38、Exatecan 和 Deruxtecan 等。例如，Enhertu是一种获批用于治疗转移性HER2阳性乳腺癌的ADC药物，载荷用的就是拓扑异构酶I抑制剂。另外一类DNA损伤剂是吡咯并苯二氮䓬类（Pyrrolobenzodiazepines, PBDs），一类从天然产物安曲霉素（anthramycin）衍生而来的DNA损伤剂。它们通过结合DNA小沟中的5′-嘌呤-鸟嘌呤-嘌呤序列，并与鸟嘌呤的外环氨基形成共价键，从而干扰DNA的正常功能。比如Tesirine（SG3199）和 Talirine 等PBDs因其高细胞毒性而被用作ADC的载荷。已上市ADC药物Zylonta载荷就是PBD。卡利霉素类（Calicheamicins）也是一类DNA损伤剂，通过结合DNA小沟，诱导双链DNA断裂，从而导致细胞死亡。例如，N-乙酰-γ-卡利霉素被用于Mylotarg和Besponsa等ADC药物的载荷。为什么理解载荷的ADME非常重要ADC的不良反应通常包括靶向作用相关的不良反应和非靶向作用相关的不良反应，其中非靶向作用相关的不良反应是决定其最大耐受剂量的主要因素。既然是非靶向作用，这些剂量限制性毒性往往与靶向的抗原和/或治疗的癌症类型无关，常常限制了ADC的剂量，使其低于能够实现最佳抗癌效果的剂量。细胞毒性药物的低皮摩尔级活性是导致ADC不良反应的重要因素，因此仅靠细胞毒性药物的活性，可能很难实现远高于1的治疗指数。因此，除了具有极高的活性外，ADC的药物载荷还必须具备适当的药物代谢和药代动力学（DMPK）特性。DMPK是药物发现过程中的重要组成部分。在过去十年中，对药物在体内的吸收、分布、代谢和排泄（ADME）以及药代动力学（PK）特性的理解，已经从描述性研究转变为定量和机制方面的理解，以了解药物在体内的过程。对于传统的口服小分子药物而言，DMPK科学家主要关注两个方面：化合物是否具有生物药剂学上合适的、可成药的药代动力学特性，以及化合物是否具有可能在临床中引发安全问题的特性。为此，清除率和生物利用度是前者的关键特征，而药物相互作用（DDIs）和代谢相关的特异性药物反应（生物活化）则是后者的首要考虑因素。在这种背景下，可以尝试将ADC药物载荷的开发重点与用于口服给药的小分子药物进行对比。载荷的溶解性对于口服小分子药物候选物需具有可接受的生物利用度。因此，在药物发现过程中，药物候选物在水性介质中的溶解性是需要优化的关键理化性质之一。一般来说，候选药物需要具有高于10μM的溶解度，才能进行临床前测试。此外，低溶解度分子的口服生物利用度通常变异比较大，且往往剂量/暴露量之间不成比例，通常需要进行制剂配方优化。不过，ADC毕竟是静脉给药，看似不涉及口服生物利用度这一问题。尽管口服吸收与ADC药物载荷无关，但仍需了解候选载荷的几个基本特性：大小、极性、亲脂性和构象动力学。这些理化性质很重要，因为药物载荷需要具有适合大规模偶联到抗体的功能基团。比如许多高活性小分子药物，缺乏所需的化学功能基团用于偶联，如果这类载荷进行修改，引入这些“反应基团”，可能会对药物载荷的活性产生不利影响。此外，除了需要具备“反应基团”外，候选载荷还必须具有足够的溶解性，因为抗体偶联过程是在水性环境中进行的。为什么不在有机溶剂中呢？因为，偶联反应中过度暴露于有机溶剂可能会使抗体变性，导致蛋白质构象变化和聚集，从而导致ADC功能丧失，并可能增加免疫原性风险。载荷渗透性和旁观者效应一般来说，小分子药物穿过脂质生物膜的能力是决定其ADME属性的关键，影响生物利用度（如穿过胃肠道上皮）或药理学特性（如穿透器官屏障），决定药物能够发挥预期的治疗效果。因此，药物的亲脂性（描述化合物在水相和脂相之间分配的指标）是药物发现过程中需考察的基本理化性质指标。对于口服给药的分子来说，渗透性是一个关键的指标，与分子口服生物利用度高低直接有关。尽管口服生物利用度对于ADC的药物载荷来说并不是一个重要考虑因素，但高渗透性这一特性仍然需要关注。因为，一些药物载荷在被内吞并杀伤肿瘤细胞后，会从最初的肿瘤细胞中逸出，并穿过邻近肿瘤细胞的细胞膜，发挥“旁观者效应”，形成不依赖TAA的肿瘤杀伤。这种杀伤效果的强弱对载荷的细胞膜渗透性就有比较高的要求。李等人（Li and others）研究了药物载荷旁观者效应对ADC疗效的药理学作用，比较了两种ADC的体内活性，这两种ADC具有相同的抗体和连接子，但药物载荷不同（MMAE和MMAF）。在这项研究中，渗透性更好的MMAE展示了对邻近肿瘤细胞的强烈旁观者杀伤作用，而膜渗透性较差的药物载荷MMAF未能在体内介导旁观者杀伤。载荷的代谢另一个支持ADC载荷选择的关键指标之一是未结合药物的清除速率。一般来说，药物在进入体内后，需要到达作用部位才能发挥其药理学效应。然而，如果药物的PK特性不理想（如高清除率和/或短半衰期），那么该分子可能无法实现预期的药效学（PD）效应。一般来说，大多数脂溶性药物首先在肝脏中被代谢，然后才能被排泄。药物的代谢可以分为I相（修饰）和II相（结合）。I相反应通过氧化、还原、水解等方式改变脂溶性药物的化学结构，使其成为更具极性的分子，通常是通过移除氢原子或添加氧原子来实现。细胞色素P450酶家族负责这些I相反应的大部分过程。利用人和动物肝脏进行的体外代谢研究，以及在临床前种属中进行的体内代谢研究，是识别药物代谢途径的主要方法。通常认为，苯甲基C-H键、烯丙基甲基和O-、N-、S-甲基基团是P450介导的药物氧化反应的敏感代谢位点。对于II相代谢，药物通过结合反应与另一分子结合，产生一种药理学上无活性且有一定水溶性的化合物，从而更容易排泄。结合机制包括甲基化、乙酰化、硫酸化、葡萄糖醛酸化以及甘氨酸或谷胱甘肽结合。小分子药物代谢的原理与ADC载荷的代谢完全相同。不过，从ADC释放的载荷不会像口服小分子药物那样经历首过消除。当然，ADC载荷会被药物代谢酶处理，并在未结合载荷消除过程中发挥重要作用。因此，除了了解载荷发生了哪些化学修饰外，还需要确定哪些药物代谢酶促进了载荷的消除。在载荷选择过程中，进行肝药酶表型研究可以帮助识别参与载荷代谢的特定酶。这些表型研究的结果可以支持后续的DDI研究。而且，ADC细胞毒性载荷的剂量反应关系陡峭和治疗指数狭窄，这一试验结果就显得尤为重要。毕竟，多药联用以及老年肿瘤患者合并其它用药，潜在的DDI风险，可能会导致载荷系统暴露量的变化，并可能在某些个体中导致严重甚至危及生命的毒性。比如ADC载荷SN-38，其常见的严重毒性包括中性粒细胞减少症和腹泻。在人体中，SN-38的消除主要通过UDP葡萄糖醛酸转移酶（UGT1A1）将药物结合成β-葡萄糖醛酸苷结合物SN-38G来实现。在临床中，由于UGT1A1个体间基因多态性，SN-38的葡萄糖醛酸化程度存在很大差异，其中具有UGT1A1*28多态性的患者对SN-38的葡萄糖醛酸化能力降低，从而导致更高的SN-38暴露量。另外，UGT活性的降低与伊立替康（SN-38的前药）观察到的毒性风险增加有关。虽然载荷的肝脏代谢表征比较重要，但成功的ADC载荷还要关注在肿瘤中的稳定性。毕竟，载荷毒素的药理学靶点在肿瘤细胞内，因此载荷在释放到细胞内后必须能够抵抗降解及随后的失活，以保持生化环境中的稳定。例如，酸敏感载荷在溶酶体中不稳定，而含有二硫键、烯烃或环氧化物等功能基团的载荷可能被酶还原或转化，从而影响载荷向其使命终点的递送。ADC的体内生命周期通常是这样的，首先被静脉注射进入系统循环，之后识别肿瘤细胞表面表达的目标抗原，并随后形成抗原-ADC复合物。接下来，整个抗原-ADC复合物通过形成有被小窝并进一步发展为早期内体，内化进入细胞内。之后，一部分ADC与FcRn结合，并被反向转运回到细胞外。剩余的抗原-ADC复合物经历早期内体成熟为晚期内体，之后与溶酶体融合，并将ADC运输到降解部位，从而释放载荷。溶酶体通过H+ -ATPase持续输入质子，维持pH值在4.5到5.0之间的酸性环境，并且还含有高浓度的蛋白水解酶，如组织蛋白酶和胶原酶。释放或游离的载荷必须成功地通过内体/溶酶体的考验，才能发挥其预期的药理学效应。载荷的未来方向ADC在实体瘤和血液瘤的全面开花，吸引了工业界和学术界的广泛关注，并开始设计下一代ADC。下一代ADC主要围绕三个核心组成部分展开，即抗体、连接子和载荷。载荷方面，两类非细胞毒性治疗药物——蛋白降解靶向嵌合体（PROTACs）和小干扰核糖核酸（siRNAs）——似乎是理想的ADC载荷。PROTACs是由针对目标蛋白（POI）的配体部分通过化学连接子与E3泛素连接酶配体连接而成的双功能化合物。这些分子的药理作用机制依赖于它们将POI和E3连接酶拉近到足够近的距离，从而触发POI的定向多泛素化和随后的蛋白酶体介导的降解。尽管PROTACs是高效的降解剂，但通常不具备组织特异性。因此，通过安装一种增强组织特异性PROTAC降解的手段（例如ADC），可以减少PROTACs的副作用，优化临床治疗窗口，从而增强其在癌症治疗中的潜力。当然，抗体与分子胶偶联也能达到类似目的。这个领域已经产生了不少的交易。2023年9月7日，Seagen与Nurix签订一项合作协议，共同开发抗体偶联降解剂（Degrader-Antibody Conjugates，DAC），Nurix将获得6000万美元的预付款，并有可能获得高达约34亿美元的多个项目的研究、开发、监管和商业里程碑付款。2023年11月，Orum公司宣布与BMS签署了一项协议，BMS以1亿美元预付款收购了Orum的靶向蛋白降解剂ORM-6151，并有望获得总交易价值约1.8亿美元的里程碑付款。2023年12月12日，C4 Therapeutics宣布与默沙东签订协议，共同开发DAC。作为合作的一部分，C4T将负责开发有效载荷；默沙东将负责抗体偶联，在药物发现阶段创建DAC。C4T将获得1000万美元的预付款；对于合作的首个靶点，C4T有望获得总计约6亿美元的里程碑付款，以及未来销售的分级特许权使用费。此外，默沙东还拥有三个合作项目的扩大选择权，倘若行使权利，C4T将有资格在整个合作中获得高达约25亿美元的潜在付款。siRNAs是一类属于小非编码核糖核酸（sncRNA）家族的药物，能够通过与mRNA的特异性序列识别来靶向并沉默特定基因表达，例如癌基因、肿瘤抑制基因和其他调控基因。siRNAs存在两点局限性，限制了其成药性。一是大小和高负电荷，使其无法通过被动摄取进入细胞；二是未修饰的siRNAs通常在生理条件下半衰期较短，因为容易被细胞外和细胞内核酸酶快速降解。然而，通过使用选定的连接子和偶联化学将这类分子与靶向大分子结合，生成一种新的ADC设计，可能会增强这类分子的成药性。引自：Beyond Cytotoxic Potency: Disposition Features Required to Design ADC Payload药理毒理开发1-6群已满，7群还有100名额，进群的加微信，备注姓名+企业名称+专长领域。比如王**+A企业+注册或毒理。名额有限，已经在1-6群的朋友就不要跨群了。

Advances span leukemia, lymphoma, myeloma, myeloproliferative neoplasms, sickle cell disease, and AI-enabled diagnostics HACKENSACK, N.J., Nov. 21, 2025 /PRNewswire/ -- Investigators from Hackensack Meridian John Theurer Cancer Center (JTCC)—a leading research partner of the NCI-designated Lombardi Comprehensive Cancer Center at Georgetown University, and number one Cancer Center in New Jersey—will present 65 studies at the 67th American Society of Hematology (ASH) Annual Meeting, taking place December 6–9, 2025, in Orlando. This represents one of JTCC's largest and most diverse scientific contributions to ASH to date, highlighting innovations in cell therapy, targeted agents, AI-driven diagnostics, stem cell transplantation, and real-world evidence across virtually every hematologic disease area. "John Theurer Cancer Center continues to help shape the future of blood cancer care," said André Goy, MD, chair, physician-in-chief and vice president of oncology at Hackensack Meridian Health. "Our teams are redefining transplantation, advancing CAR-T science, and co-leading trials testing next-generation targeted therapies and immunotherapies. The depth and breadth of our ASH presentations underscore our mission: to bring transformational science rapidly to the clinic for patients with blood cancers and other serious blood disorders." Highlights of JTCC Research to be presented at ASH 2025 can be found here. Leukemia High event-free (EFS) and overall survival (OS) after non-total body irradiation (TBI) conditioning and allogeneic hematopoietic cell transplantation (HCT) in next-generation-sequencing minimal residual disease (NGS-MRD) negative B-acute lymphoblastic leukemia (B-ALL): Results from the EndRAD trial (PTCTC ONC1701) (ABSTRACT 25-12959) A phase 2 dose confirmation trial of oral ASTX030, a combination of oral azacitidine with cedazuridine among patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia (ABSTRACT 25-7509) Ziftomenib in combination with venetoclax and azacitidine in relapsed/refractory NPM1-m or KMT2A-r acute myeloid leukemia: Updated phase 1a/b safety and clinical activity results from KOMET-007 (ABSTRACT 25-3910) MRD-guided therapy of sonrotoclax (BGB-11417) + obinutuzumab (O) in patients with treatment-naive CLL: Initial results from an ongoing phase 1/1b study, BGB-11417-101 (ABSTRACT 25-7489) Real world outcomes of bispecific T-cell engagers in plasma cell leukemia (ABSTRACT 25-4651) Etoposide can be safely removed from induction chemotherapy without impacting survival for pediatric acute myeloid leukemia – a report from the Children's oncology group study AAML1831 (ABSTRACT 25-12270) Updated response and safety analyses from a Phase 1 study of ivosidenib combined with intensive chemotherapy in patients with newly diagnosed (ND) Acute Myeloid Leukemia with isocitrate dehydrogenase (IDH)1 mutation (ABSTRACT 25-421) AI-derived prediction of response and relapse to venetoclax plus hypomethylating agent based therapy in Acute Myeloid Leukemia (ABSTRACT 25-14588) TSC-101 eliminates recipient hematopoietic cells and demonstrates potential for improved relapse-free survival in patients with AML, ALL, or MDS undergoing allogeneic HCT: Updated results from the Phase 1 (ALLOHA) trial (ABSTRACT 25-12098) Trials in progress: Design of a registrational Phase 2 trial (ALLOHA) using an external control arm for TSC-101 for prevention of relapse post allogeneic HCT in patients with ALL, AML, or MDS (ABSTRACT 25-13827) Developing artificial intelligence-based transcriptomic signature for selecting patients with HOXA-MEIS1 pathway abnormalities for the treatment with menin inhibitors (ABSTRACT 25-4126) Evaluation of ventoclax initiation prophylaxis and monitoring outcomes at each dose level and time point in patients with chronic lymphocytic leukemia: A real-world experience (ABSTRACT 25-2129) Developing transcriptomic signature for IDH1 and IDH2 acute leukemia and the demonstration of high prevalence of these signatures in mutation-negative leukemia (ABSTRACT 25-4127) Impact of DUSP22 and TP63 rearrangements in patients with ALK-negative ALCL treated with frontline BV-CH(E)P (ABSTRACT 25-1798) Harnessing repressive LEF1/ β-catenin complexes to overcome drug resistance in chronic lymphocytic leukemia (ABSTRACT 25-14485) Reducing Acute Myeloid Leukemia resistance to CAR T cell therapy by epigenetic activation of the tumor inflammasome-pyroptosis signaling (ABSTRACT 25-13458) Lymphoma Epcoritamab + R-mini-CHOP results in 2-year remissions and high MRD negativity rates in elderly patients with newly diagnosed DLBCL: Results from the EPCORE NHL-2 trial (ABSTRACT 25-3828) Epcoritamab with rituximab + lenalidomide (R2) and epcoritamab maintenance deliver deep and durable remissions in previously untreated (1L) follicular lymphoma (FL): 3-year outcomes from epcore NHL-2 arms 6 and 7 (ABSTRACT 25-2787) Liquid-biopsy mutation landscape and its concordance with skin biopsies in cutaneous T-cell lymphoma (ABSTRACT 25-2858) ZUMA-25 preliminary analysis: A Phase 2 study of brexucabtagene autoleucel (brexu-cel) in patients (Pts) with relapsed/refractory (R/R) Burkitt lymphoma (BL), substudy C (ABSTRACT 25-2841) Final results of a phase 1 trial with soquelitinib (SQL), a selective interleukin-2-inducible T cell kinase (ITK) inhibitor for treatment of relapsed/refractory (R/R) T cell lymphomas (TCL) (ABSTRACT 25-2574) Acalabrutinib plus venetoclax and rituximab in patients with treatment-naive (TN) mantle cell lymphoma (MCL): Results from the Phase 2 TrAVeRse study (ABSTRACT 25-7289) Two-year update of ZUMA-2 Cohort 3: Brexucabtagene autoleucel (Brexu-cel) in patients (pts) with relapsed/refractory mantle cell lymphoma (R/R MCL) who had not received prior Bruton tyrosine kinase inhibitor (BTKi) therapy (ABSTRACT 25-2240) Phase 2 bellwave-003 cohort f: Updated clinical outcomes of nemtabrutinib in participants with relapsed or refractory marginal zone lymphoma (ABSTRACT 25-2322) A real-world analysis of safety and outcomes with first line nivolumab in combination with doxorubicin, vinblastine, and dacarbazine (NAVD) in patients with classic Hodgkin lymphoma (cHL) – a multicenter cohort study (ABSTRACT 25-2368) Safety and efficacy of brexucabtagene autoleucel in elderly patients with relapsed or refractory Mantle Cell Lymphoma: A retrospective, multicenter, international study (ABSTRACT 25-2034) Developing artificial intelligence-based transcriptomic signature for the diagnosis of dark zone lymphoma in patients without MYC gene rearrangement (ABSTRACT 25-7855) A multicenter real-world analysis of combined chemotherapy followed by consolidative radiation versus chemotherapy alone in the management of early-stage Hodgkin lymphoma – the HODGKIN25 study (ABSTRACT 25-1471) Nivolumab with doxorubicin, vinblastine, and dacarbazine (NAVD) in older adults with classic Hodgkin lymphoma: Do S1826 results hold up in the real world? (ABSTRACT 25-7840) First-line salvage therapies in relapsed/refractory large B-cell lymphoma after second- or third-line CD19-directed CAR T-cell therapy (ABSTRACT 25-3402) Multicenter, randomized Phase II study of epcoritamab for patients with large B-cell lymphomas achieving a partial response after CD19-directed CAR T-cell therapy: Trial in progress (ABSTRACT 25-15528) Zanubrutinib + obinutuzumab + sonrotoclax in patients with treatment-naive chronic lymphocytic leukemia/small lymphocytic lymphoma (TN CLL/SLL): Initial results from an ongoing phase 1/1b study, BGB-11417-101 (ABSTRACT 25-4113) Sustained remissions beyond 4 years with epcoritamab monotherapy: Long term follow-up results from the pivotal EPCORE NHL-1 trial in patients with relapsed or refractory large B-cell lymphoma (ABSTRACT 25-7543) Multiple Myeloma Real-world outcomes with elranatamab in multiple myeloma: A multi-center analysis from the United States multiple myeloma immunotherapy consortium (ABSTRACT 25-2557) Phase 1 study of ktx-1001, a first-in-class oral MMSET/NSD2 inhibitor, demonstrates clinical activity in relapsed/refractory multiple myeloma (ABSTRACT 25-2077) Phase 2 registrational study of anitocabtagene autoleucel for the treatment of patients with relapsed and/or refractory multiple myeloma: Updated results from iMMagine--1 (ABSTRACT 25-4541) Alterations in the gut microbiome and the association of butyrate producers with progression-free survival in multiple myeloma patients undergoing autologous stem cell transplantation (ABSTRACT 25-14794) Talquetamab outcomes in relapsed/refractory myeloma with extramedullary and paraskeletal soft tissue plasmacytomas (ABSTRACT 25-7804) Safety and efficacy of talquetamab in patients with relapsed and refractory multiple myeloma (RRMM) with and without renal impairment (ABSTRACT 25-7724) Enhancing the safety of ciltacabtagene autoleucel in relapsed multiple myeloma (MM): Identification of potentially modifiable risk-factors associated with delayed neurotoxicity and non-relapse mortality (ABSTRACT 25-2357) An open-label, multi-center Phase 2 study to assess the safety and efficacy of burixafor (GPC-100) and propranolol with G-CSF for the mobilization of hematopoietic progenitor cells in patients with multiple myeloma (ABSTRACT 25-14982) Prospective real-world evaluation of SKY92 for risk stratification in multiple myeloma: Comparison with updated ims/IMWG criteria in the prommis study (ABSTRACT 25-8818) Pomalidomide salvage in T-cell engager monotherapy failures: Real-world experience with talquetamab or elranatamab with pomalidomide combinations in heavily pretreated multiple myeloma (ABSTRACT 25-10539) Prolonged elranatamab treatment interruption in patients with relapsed or refractory multiple myeloma (RRMM) is feasible: A retrospective analysis from MagnetisMM-3 (ABSTRACT 25-8338) Talquetamab, a GPRC5D×CD3 bispecific antibody, in combination with pomalidomide in patients with Relapsed/Refractory multiple myeloma: Updated safety and efficacy results from the Phase 1b monumental-2 study (ABSTRACT 25-11949) Prospective study of fluoroquinolone resistance colonization in patients undergoing autologous hematopoietic stem cell transplantation in the treatment of multiple myeloma (ABSTRACT 25-13625) Identifying high-risk profiles and adverse prognoses in relapsed/refractory multiple myeloma treated with bispecific antibodies: A real-world analysis of 943 treatment initiations (ABSTRACT 25-8860) Intratumoral cellular immunotherapy with autologous hyperactivated M1 SIRP α -low macrophages in non-Hodgkin lymphoma: Clinical results from a first-in-human Phase 1 study (ABSTRACT 25-8309) Real-world disease burden and treatment patterns among triple-class–exposed patients with relapsed/refractory multiple myeloma and extramedullary disease in the US: A retrospective analysis using Flatiron Health electronic medical records (ABSTRACT 25-9053) Shared immune features correspond to high-risk multiple myeloma across multiple human subtypes and murine models (ABSTRACT 25-13910) Real-world efficacy and safety of teclistamab in relapsed or refractory multiple myeloma: Results from 87 patients treated by the polish myeloma group (ABSTRACT 25-11305) Myeloproliferative Neoplasms Preliminary data from the Phase I/II study of nuvisertib, an oral investigational selective PIM1 inhibitor, in combination with momelotinib showed clinical responses in patients with relapsed/refractory myelofibrosis (ABSTRACT 25-3882) Safety and efficacy results from A phase 1b study of R289, a dual irak 1/4 inhibitor, in patients with Relapsed/Refractory (R/R) lower risk myelodysplastic syndrome (LR-MDS) (ABSTRACT 25-13480) Nuvisertib, an oral investigational selective PIM1 kinase inhibitor, showed clinical responses strongly correlating with cytokine modulation in patients with relapsed/refractory myelofibrosis in the ongoing global phase I/II study (ABSTRACT 25-2614) Bone marrow microenvironment overlap between vexas and myelodysplastic syndrome demonstrated by targeted transcriptomic and artificial intelligence (ABSTRACT 25-7376) Noncancerous Blood Disorders Reduced intensity haploidentical bone marrow transplantation in children with severe sickle cell disease (SCD): BMT CTN 1507 (ABSTRACT 25-11982) End-of-study results from the ICON3 pines trial, a phase 3, randomized trial of eltrombopag vs. standard first-line treatment for newly diagnosed immune thrombocytopenia in children (ABSTRACT 25-4324) The real-world safety and efficacy of BCMA-directed chimeric antigen receptor T-cell therapy in systemic AL amyloidosis (ABSTRACT 25-2732) Robust HbF induction and improvement of anemia and hemolysis with base editing in sickle cell disease: Safety and efficacy findings from the ongoing BEACON study (ABSTRACT 25-2531) Children and adolescents with sickle cell disease demonstrate improved health-related quality of life and low decisional regret after hematopoietic cell transplantation: A sickle cell transplant advocacy and research alliance (STAR) study (ABSTRACT 25-12128) Increased age-adjusted mortality rates from hemophagocytic lymphohistiocytosis (HLH), 2010-2023 (ABSTRACT 25-7365) Rapid decrease in age-adjusted mortality rates associated with ITP following eltrombopag and romiplostim approvals, but not in TMA following eculizumab approval, 1999-2023 (ABSTRACT 25-9103) Technology B- and T-cell clonality using peripheral blood cell-free RNA (cfRNA) in liquid biopsy (ABSTRACT 25-7865) Not so exclusive: Co-mutations in JAK2, MPL and CALR define distinct hematologic and clonal signatures (ABSTRACT 25-10661) Temporal control of CAR expression enables thymic generation of autoreactive T cells targeting tumor-associated antigens (ABSTRACT 25-8390) About Hackensack Meridian John Theurer Cancer Center Hackensack Meridian John Theurer Cancer Center at Hackensack University Medical Center is recognized as New Jersey's #1 cancer center in New Jersey by U.S. News & World Report. They are also the largest and most comprehensive center dedicated to diagnosis, treatment, management, research, screening, and preventive care as well as survivorship of patients with all types of cancers. The 16 specialized divisions covering the complete spectrum of cancer care have developed a close-knit team of medical, research, nursing, and support staff with specialized expertise that translates into more advanced, focused care for all patients. Each year, more people in the New Jersey/New York metropolitan area turn to John Theurer Cancer Center for cancer care than to any other facility in New Jersey. John Theurer Cancer Center is part of the NCI-designated Lombardi Comprehensive Cancer Center at Georgetown University. Housed within a 781-bed not-for-profit teaching, tertiary care, and research hospital, John Theurer Cancer Center provides state-of-the-art technological advances, compassionate care, research innovations, medical expertise, and a full range of aftercare services that distinguish John Theurer Cancer Center from other facilities. The center expanded to Jersey Shore University Medical Center, serving patients in southern New Jersey and parts of Pennsylvania. Toms River Regional Cancer Center and Saint Joseph's Health are affiliated with the cancer center. For additional information, please visit . SOURCE Hackensack Meridian John Theurer Cancer Center 21% more press release views with Request a Demo