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Choosing between intensive and less intensive front-line treatment approaches for older patients with newly diagnosed acute myeloid leukaemia
The Lancet Haematology ( IF 15.4 ) Pub Date : 2022-06-27 , DOI: 10.1016/s2352-3026(22)00167-3
Nicholas J Short 1 , Hagop Kantarjian 1
Affiliation  

The outcomes of older patients with acute myeloid leukaemia are inferior to their younger counterparts, because, in part, of a more aggressive disease biology and poorer tolerance of cytotoxic chemotherapy. Although intensive chemotherapy was historically considered the only effective treatment for these patients, many older patients are not suitable for intensive chemotherapy owing to comorbidities or general frailty. Determination of patient fitness for intensive chemotherapy is imperfect, and even older patients who appear to be suitable (also known as fit) for intensive chemotherapy can have high rates of morbidity and early and late mortality with this approach. Fortunately, the outcomes of older or unfit patients with acute myeloid leukaemia have substantially improved with the use of a hypomethylating agent plus venetoclax in the front-line setting. Although the formal approval of this combination is limited to patients aged 75 years or older, or those with a clinically significant comorbidity, the high response rates and survival improvement in these patients have led many practitioners to consider this low-intensity regimen in older patients without significant comorbidities and even in younger patients with high-risk disease features for whom the expected outcomes with intensive chemotherapy are poor. Modifications to the hypomethylating agent plus venetoclax backbone might further improve the outlook for these patients, particularly in some acute myeloid leukaemia subsets with a targetable mutation. In this Viewpoint, we review the retrospective and prospective data supporting both intensive chemotherapy and low-intensity venetoclax-based approaches in older patients with acute myeloid leukaemia. We also discuss our own approach to the management of older or unfit patients with acute myeloid leukaemia, including how cytomolecular features have a role in establishing the optimal front-line therapy.



中文翻译:

为新诊断的急性髓细胞白血病老年患者选择强化和非强化一线治疗方法

老年急性髓性白血病患者的预后不如年轻患者,部分原因是疾病生物学更具侵袭性,对细胞毒性化疗的耐受性较差。尽管强化化疗在历史上被认为是对这些患者唯一有效的治疗方法,但由于合并症或全身虚弱,许多老年患者不适合强化化疗。确定患者是否适合强化化疗是不完善的,即使是看起来适合(也称为适合)强化化疗的老年患者,使用这种方法也可能具有高发病率和早期和晚期死亡率。幸运的是,在一线环境中使用低甲基化剂加维奈托克后,老年或不健康的急性髓性白血病患者的预后得到了显着改善。虽然这种组合的正式批准仅限于 75 岁或以上的患者,或有临床显着合并症的患者,但这些患者的高反应率和生存率改善导致许多从业者考虑在老年患者中使用这种低强度方案,而无需显着的合并症,甚至在具有高风险疾病特征的年轻患者中,强化化疗的预期结果很差。对低甲基化剂加 venetoclax 骨架的修饰可能会进一步改善这些患者的前景,特别是在一些具有可靶向突变的急性髓细胞白血病亚群中。在这个观点中,我们回顾了支持强化化疗和低强度 venetoclax 治疗老年急性髓系白血病患者的回顾性和前瞻性数据。我们还讨论了我们自己管理老年或不适合急性髓性白血病患者的方法,包括细胞分子特征如何在建立最佳一线治疗中发挥作用。

更新日期:2022-06-27
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