Fleischmann Maximilian, Schnetzke Ulf, Hochhaus Andreas, Scholl Sebastian
Klinik für Innere Medizin II, Abteilung Hämatologie und Onkologie, Universitätsklinikum Jena, Am Klinikum 1, 07740 Jena, Germany.
Cancers (Basel). 2021 Nov 16;13(22):5722. doi: 10.3390/cancers13225722.
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 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.
近年来,急性髓系白血病(AML)的治疗取得了进展,多种新的治疗方案已获批准。其中大多数包括针对特定突变的方法(例如,吉列替尼用于具有激活突变的AML患者),或者仅限于特定的AML亚组,如AML-MRC(伴有髓系相关改变的AML)或治疗相关AML(CPX-351)。通过本综述,我们旨在根据最近批准的治疗策略的演变范围,全面概述当前的AML治疗。我们探讨了联合使用BCL-2抑制剂维奈克拉进行表观遗传治疗的几个方面,并深入了解对基于维奈克拉的治疗方案的耐药机制,以及如何规避原发性或继发性耐药。此外,还提供了关于AML免疫治疗现状的详细概述,介绍了有前景的概念。本综述重点关注AML治疗当前和未来概念的临床重要方面,但也将介绍不同靶向治疗的分子背景,以了解AML患者正在进行的临床试验的进展和挑战。