Contemporary Management of Acute Myeloid Leukemia: A Review.

IF 28.4 1区 医学 Q1 Biochemistry, Genetics and Molecular Biology Jama Oncology Pub Date : 2024-10-01 DOI:10.1001/jamaoncol.2024.2662
Sangeetha Venugopal, Mikkael A Sekeres
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Abstract

Importance: Acute myeloid leukemia (AML) is a clonal hematopoietic cancer that disrupts normal hematopoiesis, ultimately leading to bone marrow failure and death. The annual incidence rate of AML is 4.1 per 100 000 people in the US and is higher in patients older than 65 years. Acute myeloid leukemia includes numerous subgroups with heterogeneous molecular profiles, treatment response, and prognosis. This review discusses the evidence supporting frontline therapies in AML, the major principles that guide therapy, and progress with molecularly targeted therapy.

Observations: Acute myeloid leukemia is a genetically complex, dynamic disease. The most commonly altered genes include FLT3, NPM1, DNMT3A, IDH1, IDH2, TET2, RUNX1, NRAS, and TP53. The incidence of these alterations varies by patient age, history of antecedent hematologic cancer, and previous exposure to chemotherapy and/or radiotherapy for any cancer. Since 2010, molecular data have been incorporated into AML prognostication, gradually leading to incorporation of targeted therapies into the initial treatment approach of induction chemotherapy and subsequent management. The first molecularly targeted inhibitor, midostaurin, was approved to treat patients with AML with FLT3 variants in 2017. Since then, the understanding of the molecular pathogenesis of AML has expanded, allowing the identification of additional potential targets for drug therapy, treatment incorporation of molecularly targeted therapies (midostaurin, gilteritinib, and quizartinib targeting FLT3 variants; ivosidenib and olutasidenib targeting IDH1 variants, and enasidenib targeting IDH2), and identification of rational combination regimens. The approval of hypomethylating agents combined with venetoclax has revolutionized the therapy of AML in older adults, extending survival over monotherapy. Additionally, patients are now referred for hematopoietic cell transplant on a more rational basis.

Conclusions and relevance: In the era of genomic medicine, AML treatment is customized to the patient's comorbidities and AML genomic profile.

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急性髓性白血病的当代治疗:综述。
重要性:急性髓性白血病(AML)是一种克隆性造血癌症,会破坏正常的造血功能,最终导致骨髓衰竭和死亡。在美国,急性髓细胞白血病的年发病率为每 10 万人 4.1 例,65 岁以上的患者发病率更高。急性髓性白血病包括许多亚组,其分子特征、治疗反应和预后各不相同。本综述讨论了支持急性髓细胞白血病一线疗法的证据、指导治疗的主要原则以及分子靶向疗法的进展:急性髓性白血病是一种基因复杂、动态变化的疾病。最常见的基因改变包括FLT3、NPM1、DNMT3A、IDH1、IDH2、TET2、RUNX1、NRAS和TP53。这些基因改变的发生率因患者年龄、既往血液肿瘤病史以及曾因任何癌症接受化疗和/或放疗而异。自 2010 年以来,分子数据已被纳入急性髓细胞性白血病的预后判断,并逐渐将靶向治疗纳入诱导化疗的初始治疗方法和后续管理中。2017年,首个分子靶向抑制剂米哚妥林获批用于治疗FLT3变异型AML患者。从那时起,人们对急性髓细胞性白血病分子发病机制的认识不断扩大,从而确定了药物治疗的更多潜在靶点,治疗中纳入了分子靶向疗法(米多司林、吉尔替尼和奎沙替尼靶向FLT3变异体;伊维替尼和奥鲁替尼靶向IDH1变异体;依那西替尼靶向IDH2),并确定了合理的联合治疗方案。低甲基化药物联合 Venetoclax 的批准彻底改变了老年人急性髓细胞白血病的治疗方法,延长了单药治疗的生存期。此外,患者现在可以更合理地接受造血细胞移植:在基因组医学时代,急性髓细胞性白血病的治疗需要根据患者的合并症和急性髓细胞性白血病基因组特征进行定制。
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来源期刊
Jama Oncology
Jama Oncology Medicine-Oncology
CiteScore
37.50
自引率
1.80%
发文量
423
期刊介绍: At JAMA Oncology, our primary goal is to contribute to the advancement of oncology research and enhance patient care. As a leading journal in the field, we strive to publish influential original research, opinions, and reviews that push the boundaries of oncology science. Our mission is to serve as the definitive resource for scientists, clinicians, and trainees in oncology globally. Through our innovative and timely scientific and educational content, we aim to provide a comprehensive understanding of cancer pathogenesis and the latest treatment advancements to our readers. We are dedicated to effectively disseminating the findings of significant clinical research, major scientific breakthroughs, actionable discoveries, and state-of-the-art treatment pathways to the oncology community. Our ultimate objective is to facilitate the translation of new knowledge into tangible clinical benefits for individuals living with and surviving cancer.
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