BACKGROUND Acute myeloid leukemia (AML) is a disease of the hematopoietic system that remains a therapeutic challenge despite advances in our understanding of the underlying cancer biology in the past decade. It is also an affliction of the elderly that predominantly affects patients above 60 years of age. Standard therapy involves intensive chemotherapy that is often difficult to tolerate in older populations. Fortunately, recent developments in molecular targeting have shown promising results in treating leukemia, paving the way for novel treatment strategies that are easier to tolerate. SUMMARY Venetoclax, a BCL-2 inhibitor, when combined with a hypomethylating agent, has proven to be a highly effective and well-tolerated drug, and established itself as a new standard for treating AML in patients who are unfit for standard intensive therapy. Other targeted therapies include clinically proven and FDA approved agents, such as IDH1/2 inhibitors, FLT3 inhibitors, and Gemtuzumab, as well as newer and more experimental drugs such as magrolimab, PI-kinase inhibitors, and T-cell engaging therapy. Some of the novel agents such as magrolimab and menin inhibitors are particularly promising, providing therapeutic options to a wider population of patients than ever before. Determining who will benefit from intense or novel low intense therapy remains a challenge and it requires careful assessment of individual patient's fitness and disease characteristics. KEY MESSAGES This article reviews past and current treatment strategies that harness various mechanisms of leukemia-targeting agents and introduces novel therapies on the horizon aimed at exploring therapeutic options for elderly and unfit patient population. It also provides a strategy to select the best available therapy for elderly patients with both newly diagnosed and relapsed/refractory AML.

中文翻译：

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老年人急性髓系白血病治疗：对现在和未来的全面回顾。

背景急性髓系白血病（AML）是一种造血系统疾病，尽管在过去十年中我们对潜在癌症生物学的理解取得了进展，但它仍然是一个治疗挑战。这也是一种老年人的困扰，主要影响60岁以上的患者。标准治疗涉及强化化疗，这在老年人群中通常难以耐受。幸运的是，分子靶向的最新发展在治疗白血病方面显示出了有希望的结果，为更容易耐受的新型治疗策略铺平了道路。摘要 Venetoclax 是一种 BCL-2 抑制剂，当与低甲基化药物联合使用时，已被证明是一种高效且耐受性良好的药物，并成为治疗不适合标准强化治疗的患者的 AML 的新标准。其他靶向治疗包括经临床验证和 FDA 批准的药物，如 IDH1/2 抑制剂、FLT3 抑制剂和 Gemtuzumab，以及更新和更多实验性药物，如 Magrolimab、PI 激酶抑制剂和 T 细胞参与疗法。Magrolimab 和 menin 抑制剂等一些新型药物特别有前途，为比以往更广泛的患者群体提供了治疗选择。确定谁将从高强度或新型低强度治疗中受益仍然是一个挑战，需要仔细评估个体患者的健康和疾病特征。关键信息本文回顾了过去和当前利用白血病靶向药物的各种机制的治疗策略，并介绍了即将出现的新疗法，旨在探索针对老年和不健康患者群体的治疗选择。它还提供了一种策略，为新诊断的老年患者和复发/难治性 AML 患者选择最佳的可用疗法。