Abstract
Simple SummaryAML is a genetically heterogeneous disease with a median age of diagnosis between 60 and 70 years. Thus, many AML patients are not eligible for intensive chemotherapy. Often, the disease is accompanied by a poor prognosis due to high-risk genetic features or due to antecedent hematologic disorders (e.g., myelodysplastic syndrome). Therefore, AML treatment remains a challenge; even after intensive chemotherapy and allogeneic stem cell transplantation (alloHSCT), AML relapses are regularly observed. Thus, new concepts of AML therapy, considering tailored treatment approaches after comprehensive molecular diagnostic or implementing new immunotherapeutic strategies, are urgently needed. This review provides a detailed overview of recent developments and current promising concepts to improve the treatment and the outcome of AML patients.Treatment of acute myeloid leukemia (AML) has improved in recent years and several new therapeutic options have been approved. Most of them include mutation-specific approaches (e.g., gilteritinib for AML patients with activating FLT3 mutations), or are restricted to such defined AML subgroups, such as AML-MRC (AML with myeloid-related changes) or therapy-related AML (CPX-351). With this review, we aim to present a comprehensive overview of current AML therapy according to the evolved spectrum of recently approved treatment strategies. We address several aspects of combined epigenetic therapy with the BCL-2 inhibitor venetoclax and provide insight into mechanisms of resistance towards venetoclax-based regimens, and how primary or secondary resistance might be circumvented. Furthermore, a detailed overview on the current status of AML immunotherapy, describing promising concepts, is provided. This review focuses on clinically important aspects of current and future concepts of AML treatment, but will also present the molecular background of distinct targeted therapies, to understand the development and challenges of clinical trials ongoing in AML patients.
Highlights
Acute myeloid leukemia (AML) is a heterogenous disease with a broad spectrum of cytogenetic and molecular aberrations contributing to the definition of distinct AML subgroups
The approval of AML-targeted therapy is mostly restricted to elderly AML patients or relapsed or refractory AML (r/r AML), while only a minority of patients who are refractory to chemotherapy subsequently undergo potential curative alloHSCT
This prognostic stratification is still under debate and especially patients with FLT3ITDlow lacking a concomitant nucleophosmin 1 (NPM1) mutation are difficult to monitor for minimal residual disease (MRD) and several studies demonstrate a clinical benefit of alloHSCT in first remission of AML patients harboring FMS-like tyrosine kinase 3 (FLT3)-ITD independently of the allelic ratio (AR) of FLT3-ITD [7,8]
Summary
Acute myeloid leukemia (AML) is a heterogenous disease with a broad spectrum of cytogenetic and molecular aberrations contributing to the definition of distinct AML subgroups. The approval of AML-targeted therapy is mostly restricted to elderly AML patients or relapsed or refractory AML (r/r AML), while only a minority of patients who are refractory to chemotherapy subsequently undergo potential curative alloHSCT. Current strategies of AML precision medicine aim to target the LSC compartment, to allow longer remission and to provide the chance of further consolidation treatment. We discuss neither present treatment strategies of acute promyelocytic leukemia (APL) nor recent advances of conventional chemotherapy, including liposomal formulation of CPX-351 (Vyxeos).
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