适合和不适合新诊断的AML患者的治疗方案的最新进展。

IF 4.7 2区 医学 Q2 ONCOLOGY
Current Treatment Options in Oncology Pub Date : 2025-09-01 Epub Date: 2025-08-23 DOI:10.1007/s11864-025-01351-3
Gray H Magee, Michael R Grunwald
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引用次数: 0

摘要

观点声明:将下一代测序(NGS)和先进的细胞遗传学诊断整合到常规临床实践中,正在重塑急性髓性白血病(AML)患者的一线治疗。分子分析现在可以实现个性化的治疗策略,特别是对于携带FLT3、IDH1、IDH2、KMT2A和NPM1突变的患者。最初用于复发/难治性疾病的小分子抑制剂越来越多地用于前期治疗。然而,在诊断时进行普遍的NGS检测对于确定有资格接受这些靶向治疗的患者至关重要。在缺乏可操作突变的患者中,仍然可以使用核型异常或提示既往MDS的高风险特征来改进治疗。在我们的实践中,我们继续对fit患者使用7 + 3诱导,为flt3突变的AML添加米多舒林或quizartinib,或为表达CD33的核心结合因子(CBF) AML添加吉妥珠单抗ozogamicin。对于治疗相关性AML或骨髓增生异常相关改变的AML患者,CPX-351是我们的标准诱导方法。对于不适合的患者,我们通常提供低甲基化剂和venetoclax。在存在IDH1突变的情况下,我们考虑阿扎胞苷联合伊沃西替尼。如果venetoclax是禁忌症或不能耐受,基于突变谱的靶向治疗如gilteritinib、ivosidenib或enasidenib可能是合适的。然而,我们试图在诊断时为所有患者确定临床试验。最近更令人兴奋的进展之一是出现了针对KMT2A重排或NPM1突变患者的menin抑制剂。虽然一些药物已经获得FDA批准或在复发/难治性环境中取得突破性进展,但它们现在正作为一线选择积极研究,并取得了有希望的结果。在可行的情况下,对于有这些改变的新诊断患者,应考虑入组临床试验。随着AML治疗前景的不断发展,及时的分子表征对于优化结果和选择最合适的一线策略比以往任何时候都更加重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Updates on Therapy Options in Fit and Unfit Patients with Newly Diagnosed AML.

Opinion statement: The integration of next-generation sequencing (NGS) and advanced cytogenetic diagnostics into routine clinical practice is reshaping frontline treatment of acute myeloid leukemia (AML) in both fit and unfit patients. Molecular profiling now enables personalized treatment strategies, particularly for patients harboring mutations in FLT3, IDH1, IDH2, KMT2A, and NPM1. Small molecule inhibitors, first reserved for relapsed/refractory disease, are increasingly used in the upfront setting. However, universal NGS testing at diagnosis is critical to identify eligible patients for these targeted therapies. In patients lacking actionable mutations, treatment can still be refined using karyotypic abnormalities or high-risk features suggestive of antecedent MDS. In our practice, we continue to use 7 + 3 induction for fit patients, adding midostaurin or quizartinib for FLT3-mutated AML, or gemtuzumab ozogamicin for core binding factor (CBF) AML expressing CD33. For patients with therapy-related AML or AML with myelodysplasia-related changes, CPX-351 is our standard induction approach. For unfit patients, we generally offer hypomethylating agents with venetoclax. In the presence of IDH1 mutations, we consider azacitidine combined with ivosidenib. If venetoclax is contraindicated or not tolerated, targeted therapies such as gilteritinib, ivosidenib, or enasidenib may be appropriate based on mutation profile. However, we try to identify clinical trials for all our patients at diagnosis. One of the more exciting recent developments is the emergence of menin inhibitors for patients with KMT2A rearrangements or NPM1 mutations. While several agents have received FDA approval or breakthrough status in the relapsed/refractory setting, they are now being actively studied as frontline options with promising results. When feasible, clinical trial enrollment should be considered for newly diagnosed patients with these alterations. As the therapeutic landscape for AML continues to evolve, timely molecular characterization is more essential than ever to optimize outcomes and select the most appropriate frontline strategy.

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来源期刊
CiteScore
7.10
自引率
0.00%
发文量
113
审稿时长
>12 weeks
期刊介绍: This journal aims to review the most important, recently published treatment option advances in the field of oncology. By providing clear, insightful, balanced contributions by international experts, the journal intends to facilitate worldwide approaches to cancer treatment. We accomplish this aim by appointing international authorities to serve as Section Editors in key subject areas, such as endocrine tumors, lymphomas, neuro-oncology, and cancers of the breast, head and neck, lung, skin, gastrointestinal tract, and genitourinary region. Section Editors, in turn, select topics for which leading experts contribute comprehensive review articles that emphasize new developments and recently published papers of major importance, highlighted by annotated reference lists. We also provide commentaries from well-known oncologists, and an international Editorial Board reviews the annual table of contents, suggests articles of special interest to their country/region, and ensures that topics are current and include emerging research.
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