Microsampling for therapeutic drug monitoring of imatinib, dasatinib, nilotinib, gilteritinib, midostaurin, and venetoclax - Microsampling Oral Oncolytics

开始日期2026-02-01

申办/合作机构-

CTIS2024-512503-39-00

/ Recruiting临床4期IIT

MRD registry and multicenter, randomized controlled pragmatic trial of standard intensity versus reduced intensity consolidation treatment in MRD-negative patients with AML or CLL (RESOLVE trial).

开始日期2025-12-19

申办/合作机构-

NCT06313437

/ Recruiting临床1期IIT

A Phase I Trial of Revumenib in Combination With 7+3 (7 Days of Cytarabine and 3 Days of Daunorubicin) + Midostaurin Induction Chemotherapy for the Frontline Treatment of NPM1 and FLT3 Mutated AML

This research is being conducted to determine a safe and effective dose of revumenib that can be given in combination with standard induction (initial therapy to induce a remission) + FLT3 targeted therapy (midostaurin) and a single cycle of post-remission therapy + FLT3 targeted therapy (midostaurin) to participants with newly diagnosed Nucleophosmin (NPM1) and FMS-like tyrosine kinase 3 (FLT3) mutated Acute Myeloid Leukemia (AML).
The names of the study drugs involved in this study are:
* Revumenib (SNDX-5613) (a type of menin inhibitor)
* Midostaurin (a type of multi-kinase including FLT3 inhibitor)
* Cytarabine (a type of antineoplastic agent)
* Daunorubicin (a type of antineoplastic agent)

开始日期2024-12-06

申办/合作机构

Dana-Farber Cancer Institute, Inc.

[+1]

100 项与米哚妥林相关的临床结果

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100 项与米哚妥林相关的转化医学

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100 项与米哚妥林相关的专利（医药）

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1,210

项与米哚妥林相关的文献（医药）

2026-04-01·AMERICAN JOURNAL OF HEMATOLOGY

The Care and Cure of the Leukemias in 2026

Review

作者: Wierda, William ; Kadia, Tapan ; Kantarjian, Hagop ; Haddad, Fadi G. ; Freireich, Emil J. ; Ravandi, Farhad ; Chifotides, Helen T. ; Jabbour, Elias ; Jain, Nitin ; Welch, Mary Alma

ABSTRACT:

It is an exciting era in leukemia owing to the development of novel targeted therapies and advances in genomics, pathophysiology, prognostication, and monitoring (e.g., highly sensitive measurable residual disease assays). Currently, most leukemias are effectively treated with immunotherapies (highly effective monoclonal antibodies targeting CD19 [blinatumomab], or CD22 [inotuzumab ozogamicin]), BCR::ABL1 tyrosine kinase inhibitors (TKIs; e.g., dasatinib, ponatinib), Bruton TKIs (e.g., ibrutinib, acalabrutinib), BCL‐2 inhibitors (venetoclax), IDH1/2 inhibitors (ivosidenib, olutasidenib, and enasidenib), FLT3 inhibitors (e.g., midostaurin, quizartinib, and gilteritinib), menin inhibitors (revumenib, ziftomenib), and chimeric antigen receptor T‐cell therapies. These novel agents and their judicious use in combination strategies have transformed the treatment landscape across all leukemias, significantly increased survival and quality of life for patients, and attenuated the need for intensive chemotherapy and hematopoietic stem cell transplantation. Leukemia subtypes, such as Philadelphia‐positive acute lymphoblastic leukemia (incurable before 2000) and chronic lymphocytic leukemia (previously considered incurable) with historically dire prognoses were recently transformed to favorable leukemias with 5‐ and 10‐year survival rates of 80+% and 90+%, respectively. The BCR::ABL1 TKIs resulted in normal life expectancy in chronic myeloid leukemia. Notable advances have also been made in AML with targeted therapies, although some subsets (older/unfit patients for intensive chemotherapy, complex karyotype, TP53 ‐mutated, KMT2A ‐rearranged, and treated secondary AML) still have unfavorable outcomes. Herein, we provide a high‐level overview of prominent clinical developments across all leukemias. In contemporary times, harnessing the benefits of novel targeted therapies and the evolving treatment landscape bolster the optimistic view that most, if not all, leukemias are curable.

2026-02-17·JOURNAL OF CHEMOTHERAPY

Concurrent inhibition of FLT3 and sphingosine kinase-1 triggers synergistic cytotoxicity in midostaurin resistant FLT3-ITD positive acute myeloid leukemia cells via blocking FLT3/STAT5A signaling to induce apoptosis

Article

作者: Adan, Aysun ; Tecik, Melisa

The FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) is one of the most frequent mutations observed in acute myeloid leukemia (AML) which contributes to disease progression and unfavorable prognosis. Midostaurin, a small FLT3 inhibitor (FLT3I), is clinically approved. However, patients generally possess acquired resistance when midostaurin used alone. Shifting the balance in the sphingolipid rheostat toward anti-apoptotic sphingosine kinase-1 (SK-1) or glucosylceramide synthase (GCS) is related to therapy resistance in cancer, however, their role in midostaurin resistant FLT3-ITD positive AML has not been previously investigated. We generated midostaurin resistant MV4-11 and MOLM-13 cell lines which showed increased IC₅₀ values compared to their sensitive partner cells. SK-1 is overexpressed in resistant cells while GCS remains unchanged. Subsequent pharmacological targeting of SK-1 in resistant cells decreased SK-1 protein level, inhibited cell proliferation and showed additive or synergistic effect on cell growth, as confirmed by the Chou-Talalay combination index, and induced G0/G1 arrest (PI staining by flow cytometry). Cotreatment (SKI-II plus midostaurin) triggered apoptosis via phosphatidylserine exposure (annexin V/PI double staining). Mechanistically, induction of the intrinsic pathway of apoptosis was confirmed as increased activating cleavages of caspase-3 and PARP and increased Bax/Bcl-2 ratios. Activating phosphorylations of FLT3 (at tyrosine residue 591) and STAT5A (at tyrosine residue 694) dramatically inhibited in resistant cells treated with the combination. In conclusion, midostaurin resistance could be reversed by dual SK-1 and FLT3 inhibition in midostaurin resistant AML cell lines, providing the first evidence of a novel treatment approach to re-sensitize FLT3-ITD positive AML.

2026-02-01·Blood neoplasia

Safety of gemtuzumab ozogamicin with cytarabine, daunorubicin, and midostaurin induction in FLT3-mutated AML

Article

作者: Grieselhuber, Nicole R ; Sahasrabudhe, Kieran ; Dvorak-Kornaus, Kaitlyn M ; Behbehani, Gregory K ; Eisfeld, Ann-Kathrin ; Blachly, James S ; Borate, Uma ; Laszlo, George S ; Koenig, Kristin L ; Jain, Jayanshu ; Long, Meixiao ; Li, Junyang ; Swords, Ronan ; Srisuwananukorn, Andrew ; Walter, Roland B ; Zhao, Qiuhong ; Pugh, Kelly ; Handa, Shivani ; Mims, Alice S ; Larkin, Karilyn T M ; Saultz, Jennifer ; Cook, Rachel

This phase 1 study investigated the addition of gemtuzumab ozogamicin (GO) to intensive chemotherapy with cytarabine, daunorubicin, and midostaurin in 21 patients with newly diagnosed (ND) FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML). Four dose levels of GO were evaluated. The use of GO was tolerable, with all dose-limiting toxicities similar to those seen in standard-of-care treatment. After induction, the median time to platelet recovery was 26 days, and the median time to absolute neutrophil count (ANC) recovery was 27 days. The maximum tolerated dose was cytarabine 100 mg/m² on days 1 to 7, midostaurin 50 mg twice daily on days 8 to 21, daunorubicin 60 mg/m² on days 1 to 3, and GO 3 mg/m² on days 1 and 4. For the 18 patients who were evaluable for response after induction therapy, 16 patients (76%) achieved a composite complete response (complete remission [CR] + CR with incomplete hematologic recovery), and 2 (10%) had stable disease. Of the 14 patients who proceeded to consolidation, 5 discontinued the study for transplant, 1 for disease progression, and 1 for physician discretion. Seven patients completed consolidation therapy, all of whom achieved a CR. In total, 13 of the 21 patients (62%) received a hematopoietic stem cell transplant. Our results show that GO can safely be combined with intensive chemotherapy with midostaurin in ND, FLT3-mutated AML. This trial was registered at www.clinicaltrials.gov as #NCT03900949.

102

项与米哚妥林相关的新闻（医药）

2026-03-24

·allsci.com

Yatiri Bio options global rights to Oscotec’s multikinase inhibitor denfivontinib for AML

Yatiri Bio, a San Diego-based precision medicine company, has entered an exclusive global option to in-license agreement with South Korea’s Oscotec for denfivontinib (G-749; SKI-G-801), a multikinase inhibitor, for the treatment of acute myeloid leukemia. Under the deal terms, Yatiri holds the exclusive option to license denfivontinib for development and commercialization worldwide.. Financial terms were not disclosed. Denfivontinib is a small molecule multikinase inhibitor described by Oscotec as being an FLT3/AXL dual inhibitor. FLT3 is a receptor tyrosine kinase frequently mutated in AML and a validated therapeutic target. Preclinical evidence shows the molecule targets both wild-type and mutant forms (notably FLT3-ITD and FLT3-D835Y), while there is also evidence suggesting potential activity against other kinases. Oscotec completed a Phase I trial in relapsed/refractory AML (NCT03564288), enrolling 14 patients between 2018 and 2021. A separate Phase I trial in advanced solid tumors (NCT05971862) was conducted at Yonsei University in Seoul. Yatiri plans to apply its proprietary ProteoCharts platform to identify a biomarker profile for denfivontinib AML treatment that extends beyond standard FLT3 mutation status. The platform uses deep neural networks to integrate proteomic profiling with clinical data and functional testing in patient-derived models. The company states it has identified a responder population that is FLT3-independent, potentially broadening the eligible patient pool beyond mutation-targeted therapies. The AML treatment landscape for FLT3-targeted therapies includes several approved agents and established acute myeloid leukemia biomarkers based on genomic mutation testing: Midostaurin (Rydapt) — Novartis — approved for FLT3-mutant AML Gilteritinib (Xospata) — Astellas — approved for relapsed/refractory FLT3-mutant AML Quizartinib (Vanflyta) — Daiichi Sankyo — approved 2023 for newly diagnosed FLT3-ITD-positive AML All three rely on DNA-based companion diagnostics for patient selection. Yatiri Bio’s thesis is that proteomic stratification can identify responding populations that genomic testing misses. Your email address will not be published. Required fields are marked * Comment * Name * Email * Website

临床1期引进/卖出上市批准

2026-03-18

·今日头条

急性髓系白血病治疗方案演变：从细胞毒治疗到精准医学的循证综述

摘要急性髓系白血病是一种起源于造血干细胞的恶性克隆性疾病。其治疗在过去几十年中经历了从以标准剂量阿糖胞苷联合蒽环类药物为基础的“3+7”方案，到针对特定分子亚型的靶向治疗，再到近年来兴起的免疫治疗和新型药物联合方案的重大演变。本文系统综述了近几十年来急性髓系白血病治疗方案的变迁，深入分析了各阶段代表性方案的疗效、优势及局限性，并探讨了当前精准医学时代下的治疗策略与未来发展方向。针对急性早幼粒细胞白血病t(15;17)染色体易位的ARRA和ATO的无化疗方案下一篇专门介绍关键词急性髓系白血病；治疗方案；3+7方案；靶向治疗；免疫治疗；精准医学引言急性髓系白血病是成年人中最常见的急性白血病类型，其特征为骨髓中髓系原始细胞异常增殖并抑制正常造血。在过去几十年中，急性髓系白血病的治疗策略经历了显著的演变。早期主要依赖于非特异性的细胞毒化疗，随后逐渐引入了造血干细胞移植以巩固疗效。近年来，随着对急性髓系白血病分子发病机制的深入理解，靶向治疗和免疫治疗取得了突破性进展，彻底改变了治疗格局。本文旨在通过详实的数据和循证医学证据，系统阐述急性髓系白血病治疗方案的变迁历程，对比分析各方案的优劣，为临床实践和未来研究提供参考。一、传统化疗时代：奠基与优化 1. “3+7”方案的建立与标准地位 • 方案组成与原理：自20世纪70年代以来，以阿糖胞苷为基础的联合化疗成为急性髓系白血病治疗的基石。其中，最经典的“3+7”方案由柔红霉素或去甲氧柔红霉素联合阿糖胞苷组成，即柔红霉素连续输注3天，阿糖胞苷连续输注7天。该方案通过协同作用，有效杀伤增殖期的白血病细胞。 • 临床疗效数据：多项大规模临床试验证实了“3+7”方案的高效性。例如，在英国医学研究委员会的AML10试验中，采用该方案诱导治疗的初治患者，完全缓解率可达60%–80%。对于年龄小于60岁的患者，长期无病生存率约为30%–40%。 • 方案优势：该方案疗效确切，应用广泛，是后续所有新药研发的对照标准。其药物可及性高，成本相对较低，适用于大多数不具备特定分子标志物的患者。 2. 剂量优化与药物替代 • 阿糖胞苷剂量的探索：为提高疗效，研究者探索了不同剂量的阿糖胞苷。高剂量阿糖胞苷在巩固治疗中显示出优于标准剂量的无复发生存率，特别是在核心结合因子急性髓系白血病患者中。然而，在诱导治疗中，高剂量并未显著提高完全缓解率，且伴随更严重的骨髓抑制和感染风险。 • 蒽环类药物的选择：在“3+7”框架内，去甲氧柔红霉素因其更长的半衰期和更强的细胞内摄取能力，在多项研究中显示出优于柔红霉素的疗效。荟萃分析表明，使用去甲氧柔红霉素可显著提高年轻患者的总生存率，尤其是在年龄小于50岁的群体中。 3. 老年及不适合强化疗患者的方案 • 低强度化疗：对于年龄大于60岁或伴有严重合并症的患者，标准“3+7”方案的毒性难以耐受。因此，开发了以低剂量阿糖胞苷为基础的方案，或使用阿扎胞苷、地西他滨等去甲基化药物。这些方案虽然完全缓解率较低（约15%–30%），但显著改善了患者的生存质量并延长了总生存期。 • 局限性：传统化疗方案的主要局限在于其非特异性，对正常造血干细胞同样具有毒性，导致长期骨髓抑制和感染风险。此外，对于具有不良预后细胞遗传学或分子特征的患者，单纯化疗的疗效有限，复发率高。二、造血干细胞移植的应用与地位演变 1. 移植作为巩固治疗的标准 • 原理与时机：在患者达到第一次完全缓解后，进行异基因造血干细胞移植被认为是目前唯一可能实现长期治愈的手段。移植通过高剂量化疗或放疗清除残存的白血病细胞，并利用供者的免疫系统产生移植物抗白血病效应。 • 疗效数据：对于中高危急性髓系白血病患者，移植后5年无复发生存率可达40%–60%，显著优于单纯化疗巩固。然而，移植相关死亡率约为10%–20%，且存在慢性移植物抗宿主病等长期并发症。 2. 移植适应症的精准化 • 风险分层指导：随着分子遗传学的发展，移植的适应症逐渐从“所有适合患者”转向基于风险分层的精准选择。例如，对于具有良好预后核型（如t(8;21)、inv(16)）的患者，单纯化疗联合高剂量阿糖胞苷巩固即可获得良好疗效，移植的获益有限。而对于具有不良预后核型（如复杂核型、-7、-5）的患者，移植是首选巩固策略。 • 微小残留病的指导作用：近年来，微小残留病的检测成为指导移植决策的重要工具。在第一次完全缓解期，若微小残留病持续阳性，提示复发风险极高，应强烈推荐移植；反之，若微小残留病阴性，可考虑避免移植以减少相关风险。三、靶向治疗的突破与精准医学时代 1. FLT3抑制剂的应用 • FLT3-ITD突变的临床意义：FLT3内部串联重复突变是急性髓系白血病最常见的分子异常之一，见于约25%的患者，与高白细胞计数、高复发率和不良预后密切相关。 • 第一代与第二代抑制剂：早期的FLT3抑制剂如米哚妥林在联合“3+7”方案的III期临床试验（RATIFY）中，显示出显著的总生存获益，使米哚妥林联合化疗成为新诊断FLT3突变急性髓系白血病患者的标准治疗。然而，单药疗效有限，且易产生耐药。 • 后续治疗与耐药克服：吉瑞替尼作为高选择性的第二代FLT3抑制剂，在复发难治性患者中显示出高达50%的完全缓解率，并显著延长了总生存期。特别是对于移植后复发的患者，吉瑞替尼提供了有效的挽救治疗选择。 2. IDH1/2抑制剂的进展 • IDH突变的致病机制：异柠檬酸脱氢酶1/2突变导致代谢产物2-羟戊二酸积累，抑制组蛋白和DNA去甲基化，阻断细胞分化。 • 艾伏尼布与恩西地平：艾伏尼布（针对IDH1）和恩西地平（针对IDH2）通过抑制突变酶活性，促进白血病细胞分化成熟。在单药治疗复发难治性患者的研究中，艾伏尼布的完全缓解率约为30%，且安全性良好。目前，这些药物正在探索与阿扎胞苷或化疗的联合应用，以期在初治患者中取得更佳疗效。 3. BCL-2抑制剂：维奈克拉的革命性影响 • 作用机制：维奈克拉选择性抑制BCL-2蛋白，解除其对线粒体凋亡通路的抑制，从而诱导白血病细胞凋亡。急性髓系白血病细胞高度依赖BCL-2维持生存。 • 联合去甲基化药物：在不适合强化疗的老年患者中，维奈克拉联合阿扎胞苷或地西他滨的方案取得了突破性进展。VIALE-A试验显示，该联合方案的完全缓解/伴不完全血液学恢复的完全缓解率高达66.4%，显著优于单用去甲基化药物，并显著延长了总生存期。这一结果确立了该方案在老年急性髓系白血病治疗中的标准地位。 • 向年轻患者及巩固治疗的拓展：目前，维奈克拉联合强化疗的方案正在年轻患者中进行临床试验，初步结果显示了极高的微小残留病阴性率，提示其可能进一步提高治愈率。此外，维奈克拉作为移植后的维持治疗也显示出减少复发的潜力。 4. 其他靶点与药物 • 靶向CD33的吉妥珠单抗奥佐米星：作为一种抗体药物偶联物，吉妥珠单抗奥佐米星在特定亚型（如核心结合因子急性髓系白血病）中显示出疗效，但其应用受限于肝毒性风险。 • 靶向CD47的药物：CD47是“别吃我”信号分子，其抑制剂可增强巨噬细胞对白血病细胞的吞噬作用，目前正处于临床开发阶段。四、免疫治疗的探索与挑战 1. 过继性细胞治疗 • CAR-T细胞疗法：虽然在急性淋巴细胞白血病中取得巨大成功，但CAR-T在急性髓系白血病中的应用面临挑战，主要原因是缺乏特异性的肿瘤相关抗原，导致“靶向/非靶向”毒性风险高。目前，针对CD123、CLEC12A等靶点的CAR-T正在临床试验中，初步结果显示一定的抗白血病活性，但仍需解决安全性问题。 • 自然杀伤细胞治疗：自然杀伤细胞具有天然的抗肿瘤活性，且移植物抗宿主病风险较低。同种异体自然杀伤细胞输注在急性髓系白血病患者中显示出安全性和初步疗效，特别是在移植后微小残留病阳性的患者中。 2. 免疫检查点抑制剂 • PD-1/PD-L1通路：急性髓系白血病细胞常高表达PD-L1，抑制T细胞功能。然而，单药使用PD-1抑制剂在急性髓系白血病中疗效有限，可能与其免疫抑制性的肿瘤微环境有关。目前的研究主要集中在联合用药，如与去甲基化药物或FLT3抑制剂联用，以期逆转免疫逃逸。五、当前治疗策略的整合与个体化 1. 基于年龄和体能状态的分层治疗 • 年轻适合患者（<60岁）：首选以“3+7”为基础的强化疗，根据分子遗传学结果加入靶向药物（如FLT3抑制剂、吉妥珠单抗奥佐米星）。达到完全缓解后，依据风险分层和微小残留病状态决定是否进行造血干细胞移植。 • 老年或不适合强化疗患者（≥60岁）：首选维奈克拉联合去甲基化药物，或低强度化疗。对于特定靶点突变的患者，可考虑IDH抑制剂或FLT3抑制剂单药或联合治疗。 2. 基于分子遗传学特征的精准治疗 • 良好预后组：如核心结合因子急性髓系白血病，强化疗联合靶向巩固可获得高治愈率，移植仅用于高危或复发患者。 • 中等预后组：根据具体突变选择靶向药物，并积极评估移植指征。 • 不良预后组：首选新药临床试验或异基因造血干细胞移植。 3. 微小残留病的动态监测与干预 • 检测技术：流式细胞术、PCR和NGS技术的发展使得微小残留病检测的灵敏度达到10^-4至10^-6。 • 临床应用：微小残留病状态是独立于遗传学的预后因素。持续微小残留病阴性提示长期缓解，而微小残留病转阳则强烈提示即将复发，需提前干预，如停用免疫抑制剂、供者淋巴细胞输注或启动挽救治疗。六、挑战与未来展望 1. 当前治疗面临的挑战 • 耐药与复发机制：尽管靶向治疗有效，但耐药仍是主要问题。如FLT3抑制剂的耐药常由二次突变或旁路激活引起。深入理解耐药机制是开发下一代药物的关键。 • 药物可及性与成本：新型靶向药物和免疫治疗价格昂贵，限制了其在资源有限地区的应用。如何平衡疗效与成本是全球性挑战。 • 老年患者的治疗优化：老年急性髓系白血病异质性大，如何精准评估体能状态和合并症，制定个体化治疗方案仍是难点。 2. 未来发展方向 • 新型药物组合：探索靶向药物与化疗、免疫治疗的最优组合，以期达到协同增效、克服耐药的目的。例如，维奈克拉+FLT3抑制剂+去甲基化药物的三联疗法正在临床试验中。 • 表观遗传学治疗的深化：除DNA甲基化外，组蛋白修饰、RNA甲基化等表观遗传调控机制为新药开发提供了新靶点。 • 人工智能与精准医疗：利用人工智能分析大规模基因组和临床数据，构建预测模型，实现更精准的预后分层和治疗方案推荐。七、结论急性髓系白血病的治疗在过去几十年中经历了从传统化疗到精准靶向、免疫治疗的深刻变革。虽然“3+7”方案仍是基础，但FLT3抑制剂、IDH抑制剂和维奈克拉等新药的加入显著改善了特定人群的预后。造血干细胞移植的地位在精准分层指导下更加明确。当前的治疗策略强调基于年龄、体能状态、分子遗传学和微小残留病的个体化综合治疗。未来，通过深入理解疾病生物学、开发新型药物组合和应用人工智能技术，有望进一步提高治愈率，实现真正的精准医疗。参考文献 [1] Döhner H, et al. Diagnosis and management of AML in adults: 2022 ELN recommendations from an international expert panel. Blood. 2022. [2] Stone RM, et al. Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with FLT3 Mutations. N Engl J Med. 2017. [3] DiNardo CD, et al. Venetoclax Combined with Decitabine or Azacitidine in Treatment-Naive, Elderly Patients with Acute Myeloid Leukemia. Blood. 2018. [4] Perl AE, et al. Selective Inhibition of FLT3 by Gilteritinib in Relapsed or Refractory AML. N Engl J Med. 2019. [5] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Acute Myeloid Leukemia. （注：以上综述基于近几十年来急性髓系白血病治疗领域的关键临床试验和指南更新，数据和结论均源自权威医学文献和数据库，未作任何编造。）注：针对急性早幼粒细胞白血病t(15;17)染色体易位的ARRA和ATO的无化疗方案下一篇专门介绍

2026-03-09

·newsroom.astellas.com

Astellas and Hovon Confirm Phase 3 Study Did not Meet its Primary Endpoint of Overall Survival in Patients with Newly Diagnosed FLT3m+ AML

TOKYO AND ROTTERDAM, March 9, 2026 – Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, “Astellas”) and HOVON Foundation (Rotterdam, The Netherlands) today announced that the Phase 3 HOVON 156 / AMLSG 28-18 / PASHA study investigating XOSPATA™ (gilteritinib) versus midostaurin-based treatment in patients with newly diagnosed FLT3-mutated acute myeloid leukemia (FLT3m+ AML) eligible for intensive chemotherapy did not meet its primary endpoint of overall survival (OS) at the primary analysis. While the study did not meet its primary endpoint of OS, gilteritinib showed a comparable OS benefit to midostaurin-based treatment in newly diagnosed FLT3m+ AML. The rates of treatment emergent adverse events and grade 3 or higher adverse events were similar between both treatment arms. Astellas and HOVON will complete a full evaluation of the data from HOVON 156 / AMLSG 28-18 / PASHA, including secondary endpoints, subgroup analysis and the safety of gilteritinib in combination with chemotherapy, and work with investigators on the future dissemination of the results. Moitreyee Chatterjee-Kishore, PhD, MBA, Head of Oncology Development, Astellas “Whilst we are disappointed that the study did not meet its primary endpoint, we extend our thanks to all study participants for their contributions. Astellas remains committed to advancing FLT3-targeted research to improve outcomes across the AML treatment landscape.” Marleen C. Breems-de Ridder, PhD, CEO, HOVON Foundation “Even when research findings are disappointing, we know that they provide important contributions to our collective understanding. We will continue our mission to conduct rigorous clinical research to improve outcomes for patients with hematologic diseases. HOVON and AMLSG would like to express their gratitude to participating patients and all investigators and collaborative groups conducting this collaborative academic study.” Astellas expects this result to have a minor impact on its financial results for the fiscal year ending March 31, 2026. Gilteritinib is a FLT3 inhibitor with demonstrated activity against FLT3-ITD, a common driver mutation that presents with a high disease burden and poor prognosis, and FLT3-tyrosine kinase domain (TKD) mutations.1 Gilteritinib is available as XOSPATA™ across the world, including in the U.S., Japan, China and multiple European countries for the treatment of adult patients who have relapsed or refractory FLT3+ AML. About Gilteritinib Gilteritinib is an FMS-like tyrosine kinase 3 (FLT3) inhibitor with demonstrated activity against FLT3-ITD, a common driver mutation that presents with a high disease burden and poor prognosis, and FLT3-TKD mutations.1 It was discovered through a research collaboration with Kotobuki Pharmaceutical Co., Ltd., and Astellas has exclusive global development, commercialization and manufacturing rights to gilteritinib.2 Gilteritinib was evaluated in ADMIRAL (NCT02421939), a Phase 3, open-label, multicenter, randomized clinical trial comparing gilteritinib with prespecified salvage chemotherapy in adult patients with relapsed or refractory FLT3-mutated AML.3 About Acute Myeloid Leukemia (AML) Acute myeloid leukemia (AML) is an aggressive cancer that affects the bone marrow and blood, and its incidence increases with age.4,5 Of patients newly diagnosed with AML and tested for FLT3 mutations, approximately one-third have an alteration to the FLT3 gene. FLT3-ITD mutations have been associated with worsened disease-free survival and overall survival, and a higher risk of getting the disease more than once. FLT3 mutation status can change over the course of AML treatment, even after relapse.6-9 About Astellas Astellas is a global life sciences company committed to turning innovative science into VALUE for patients. We provide transformative therapies in disease areas that include oncology, ophthalmology, urology, immunology and women's health. Through our research and development programs, we are pioneering new healthcare solutions for diseases with high unmet medical need. Learn more at www.astellas.com. About HOVON Foundation The HOVON‑AMLSG consortium brought the HOVON 156 / AMLSG 28‑18 trial to fruition under HOVON sponsorship through the collaboration with the collaborative leukaemia working groups from: Australia (ALLG), Austria & Germany (AMLSG), Belgium & Netherlands (HOVON), Finland–Norway–Sweden (Nordic AML), France (ALFA & FILO), Ireland (Cancer Trials Ireland), Lithuania, Spain (CETLAM), and Switzerland (SAKK). This broad international academic partnership exemplifies the strength of unified scientific effort in advancing AML research. Cautionary Notes In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties. Information about pharmaceutical products (including products currently in development) which is included in this press release is not intended to constitute an advertisement or medical advice. Contacts for inquiries or additional information: Elysia Wood elysia.wood@astellas.com Astellas Pharma Inc. Corporate Communications +81-3-3244-3201 References 1. Daver N, Schlenk RF, Russel NH, et al. Targeting FLT3 mutations in AML: review of current knowledge and evidence. Leukemia. 2019;33,299-312. 2. Data on file. Northbrook, Ill. Astellas Pharma US Inc. 3. CT.gov. A Study of ASP2215 Versus Salvage Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FMS-like Tyrosine Kinase (FLT3) Mutation. Available at: https://clinicaltrials.gov/study/NCT02421939. Last accessed: March 2026. 4. American Cancer Society. What Is Acute Myeloid Leukemia (AML)? Available at: https://www.cancer.org/cancer/acute-myeloid-leukemia/about/what-is-aml.html. Last accessed: March 2026. 5. American Cancer Society. Key Statistics for Acute Myeloid Leukemia (AML). Available at: https://www.cancer.org/cancer/acute-myeloid-leukemia/about/key-statistics.html. Last accessed: March 2026. 6. Whitman SP, Maharry K, Radmacher MD, et al. FLT3 internal tandem duplication associates with adverse outcome and gene- and microRNA-expression signatures in patients 60 years of age or older with primary cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. Blood. 2010;116(18),3622-3626. 7. Whitman SP, Archer KJ, Feng L, et al. Absence of the wild-type allele predicts poor prognosis in adult de novo acute myeloid leukemia with normal cytogenetics and the internal tandem duplication of FLT3: a Cancer and Leukemia Group B study. Cancer Res. 2001;61(19),7233-7239. 8. Visser O, Trama A, Maynadié M, et al. Incidence, survival and prevalence of myeloid malignancies in Europe. Eur J Cancer. 2012;48,3257-3266. 9. Warren M, Luthra R, Yin CC, et al. Clinical impact of change of FLT3 mutation status in acute myeloid leukemia patients. Mod Pathol. 2012;25(10):1405-12.

临床结果临床3期ASH会议

100 项与米哚妥林相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D05029	米哚妥林	L01XE39	DB06595

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
侵袭性系统性肥大细胞增多症	韩国	Novartis Korea Ltd.	2019-02-14
FLT3阳性急性髓性白血病	欧盟	Novartis Europharm Ltd.	2017-09-18
FLT3阳性急性髓性白血病	冰岛	Novartis Europharm Ltd.	2017-09-18
FLT3阳性急性髓性白血病	列支敦士登	Novartis Europharm Ltd.	2017-09-18
FLT3阳性急性髓性白血病	挪威	Novartis Europharm Ltd.	2017-09-18
肥大细胞白血病	欧盟	Novartis Europharm Ltd.	2017-09-18
肥大细胞白血病	冰岛	Novartis Europharm Ltd.	2017-09-18
肥大细胞白血病	列支敦士登	Novartis Europharm Ltd.	2017-09-18
肥大细胞白血病	挪威	Novartis Europharm Ltd.	2017-09-18
急性髓性白血病	美国	Novartis Pharmaceuticals Corp.	2017-04-28
系统性肥大细胞增多症	美国	Novartis Pharmaceuticals Corp.	2017-04-28

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
急性早幼粒细胞白血病	临床3期	美国	Novartis Pharmaceuticals Corp.	2018-07-20
急性早幼粒细胞白血病	临床3期	日本	Novartis Pharmaceuticals Corp.	2018-07-20
急性早幼粒细胞白血病	临床3期	阿根廷	Novartis Pharmaceuticals Corp.	2018-07-20
急性早幼粒细胞白血病	临床3期	澳大利亚	Novartis Pharmaceuticals Corp.	2018-07-20
急性早幼粒细胞白血病	临床3期	奥地利	Novartis Pharmaceuticals Corp.	2018-07-20
急性早幼粒细胞白血病	临床3期	比利时	Novartis Pharmaceuticals Corp.	2018-07-20
急性早幼粒细胞白血病	临床3期	巴西	Novartis Pharmaceuticals Corp.	2018-07-20
急性早幼粒细胞白血病	临床3期	保加利亚	Novartis Pharmaceuticals Corp.	2018-07-20
急性早幼粒细胞白血病	临床3期	捷克	Novartis Pharmaceuticals Corp.	2018-07-20
急性早幼粒细胞白血病	临床3期	法国	Novartis Pharmaceuticals Corp.	2018-07-20

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临床结果

适应症

分期

评价

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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


PS1846 (EHA2025)	N/A	侵袭性系统性肥大细胞增多症一线 elevated serum tryptase	125	Midostaurin 100 mg BID	選構製壓顧糧積齋壓鬱(夢製鑰淵網觸網簾顧觸) = 7/46, 14% pts experienced a discontinuation syndrome after stopping midostaurin. The most commonly reported symptoms included fatigue, peripheral edema, pleural effusion, and diarrhea 選築遞網築艱膚選觸觸 (艱餘簾構窪獵膚醖繭窪 ) 更多	-	2025-05-14
				Midostaurin <100 mg BID
NCT03280030 (CTgov)	临床2期	伴有 FLT3/ITD 突变的急性髓系白血病 \| FLT3阳性急性髓性白血病	67	Midostaurin (Midostaurin: Part 1 (Japan Only))	鏇齋鏇鏇網觸窪選衊齋 = 鹽醖製鏇積繭築廠餘鑰衊鬱觸衊鑰蓋鹹蓋齋糧 (簾夢夢壓簾繭選願鬱糧, 遞憲選夢鬱醖餘壓窪衊 ~ 遞獵鑰憲餘遞範壓糧醖) 更多	-	2025-02-11
				Midostaurin (Midostaurin: Part 2)	醖窪顧網選窪觸鹹蓋艱(網廠構淵積簾蓋願範鏇) = 願選艱淵餘構憲鬱襯獵醖淵顧衊製願襯壓觸願 (選網選齋餘鹹醖餘膚廠, 艱餘鬱蓋衊願製蓋選選 ~ 憲糧鹽顧鬱築獵糧膚鬱) 更多
ASH2024	N/A	伴有 FLT3/ITD 突变的急性髓系白血病	-	Midostaurin	範顧窪鏇獵顧鹹繭夢鹽(憲艱觸範淵衊艱鑰觸齋) = 積餘淵襯鏇顧獵願夢鏇網築衊選簾選鹹壓廠積 (衊憲鹽蓋鑰襯鑰膚觸鑰 ) 更多	-	2024-12-09
				Quizartinib	範顧窪鏇獵顧鹹繭夢鹽(憲艱觸範淵衊艱鑰觸齋) = 衊膚餘衊蓋遞壓範願繭網築衊選簾選鹹壓廠積 (衊憲鹽蓋鑰襯鑰膚觸鑰 ) 更多
NCT03836209 (Precog 0905, ASH2024) 人工标引	临床2期	急性髓性白血病一线 FLT3 Mutation	177	Gilteritinib	夢製蓋積願顧壓鏇鹹鑰(鬱夢衊醖網齋夢積窪蓋) = 壓壓製鏇鹽齋夢遞簾膚糧廠鬱鑰襯遞鬱網艱艱 (衊鹽簾襯壓蓋製鏇餘鏇 ) 更多	积极	2024-12-07
				Midostaurin	夢製蓋積願顧壓鏇鹹鑰(鬱夢衊醖網齋夢積窪蓋) = 遞鏇積顧壓鏇壓憲鹹鑰糧廠鬱鑰襯遞鬱網艱艱 (衊鹽簾襯壓蓋製鏇餘鏇 ) 更多
CALGB 10603/Ratify (ASH2024)	N/A	FLT3-TKD \| FLT3-ITD	717	Midostaurin	鏇選蓋鏇顧製糧艱築艱(選願積壓鑰艱鹹積鹽壓) = 簾夢繭獵鑰醖窪鏇壓艱淵窪壓獵蓋鑰醖願鏇鏇 (艱簾範醖醖鹹淵憲遞餘, 38.7 ~ 49.3) 更多	积极	2024-12-07
				Placebo	鏇選蓋鏇顧製糧艱築艱(選願積壓鑰艱鹹積鹽壓) = 顧積窪選夢憲壓壓餘築淵窪壓獵蓋鑰醖願鏇鏇 (艱簾範醖醖鹹淵憲遞餘, 33.6 ~ 44.4) 更多
NCT04097470 (HOVON155, Pubmed)	临床2期	骨髓增生异常/骨髓增生性疾病	140	地西他滨	膚廠廠願餘網齋鬱壓築(餘鹽膚鹽築構顧衊製製) = 廠觸製構齋獵積獵餘糧構襯積襯構鏇餘鏇廠窪 (範蓋範窪選淵網觸淵觸 ) 更多	不佳	2024-10-05
				地西他滨+米哚妥林	膚廠廠願餘網齋鬱壓築(餘鹽膚鹽築構顧衊製製) = 構觸襯範鏇餘遞遞築願構襯積襯構鏇餘鏇廠窪 (範蓋範窪選淵網觸淵觸 ) 更多
MDAAML-2018-06 (SOHO2024)	临床3期	一线	175	Midostaurin plus Intensive Chemotherapy	鑰餘艱憲餘淵艱顧鏇簾(遞觸築窪顧衊憲鹽夢積) = 26 pts (14.8%) had Midos interruption 憲齋鹹網膚廠願衊艱夢 (獵憲壓醖襯蓋淵膚艱範 ) 更多	积极	2024-09-04
RATIFY trial (EHA2024)	N/A	伴有 FLT3/ITD 突变的急性髓系白血病一线 FLT3 mutations	76	Midostaurin plus intensive chemotherapy since induction	夢顧積蓋遞願醖範願廠(願齋鑰膚廠鏇鏇窪襯網) = 顧積壓顧憲製憲壓鏇夢淵繭築憲網襯築獵簾獵 (廠鹽艱餘鹽淵膚願窪膚 ) 更多	积极	2024-05-14
				Midostaurin plus intensive chemotherapy since consolidation	觸醖構範齋獵襯鏇繭獵(醖範膚積選鏇繭構醖糧) = 憲襯憲壓憲鏇鏇淵艱觸繭膚獵襯餘艱築鑰遞衊 (醖範築壓鏇構糧衊積選 )
EHA2024	N/A	侵袭性系统性肥大细胞增多症 c-KIT D816V mutation	12	Midostaurin 100 mg twice daily	鑰構製壓艱蓋鏇遞網憲(觸襯構製廠繭鬱獵獵鑰) = 鬱廠製醖餘選窪艱築夢齋憲觸網獵獵廠鏇觸鹹 (鹹構艱範憲淵製鬱醖築 ) 更多	积极	2024-05-14