{"title":"Updates on Therapy Options in Fit and Unfit Patients with Newly Diagnosed AML.","authors":"Gray H Magee, Michael R Grunwald","doi":"10.1007/s11864-025-01351-3","DOIUrl":null,"url":null,"abstract":"<p><strong>Opinion statement: </strong>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.</p>","PeriodicalId":50600,"journal":{"name":"Current Treatment Options in Oncology","volume":" ","pages":"829-840"},"PeriodicalIF":4.7000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449387/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Treatment Options in Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11864-025-01351-3","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/23 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
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.