Division of Hematology-Oncology/Department of Medicine, University of Pennsylvania, Philadelphia, PA.
Haematologica. 2021 Oct 1;106(10):2544-2554. doi: 10.3324/haematol.2020.269134.
Intensive chemotherapy has been the backbone of the treatment of acute myeloid leukemia (AML) for decades. However, an increase in novel targeted agents, which has been brought about in part by a deeper understanding of the genetic makeup of AML, has led to remission-inducing regimens that do not require traditional cytotoxic agents. Combinations of a hypomethylating agent (HMA) and venetoclax have doubled the chance of remission for patients considered unfit for induction chemotherapy who would have traditionally been offered singleagent HMA. In fact, this regimen may rival the complete remission rate achieved with induction chemotherapy for certain populations such as the very elderly and those with secondary AML, but equivalency has yet to be established. Further advances include the addition of gemtuzumab ozogamicin and FLT3 inhibitors to induction chemotherapy, which improves survival for patients with core-binding factor and FLT3-mutated AML, respectively. Still, much work is needed to improve the outcomes of the highest-risk subgroups: frail patients and those with high-risk cytogenetics and/or TP53 mutations. Promisingly, the landscape of AML therapy is shifting dramatically and no longer is intensity, when feasible, always the best answer for AML.
几十年来，强化化疗一直是急性髓系白血病（AML）治疗的基础。然而，新型靶向药物的增加，部分原因是对 AML 遗传结构的深入了解，使得诱导缓解方案不再需要传统的细胞毒性药物。低甲基化剂（HMA）和 venetoclax 的联合使用，使那些传统上接受单一 HMA 治疗的不适合诱导化疗的患者的缓解机会增加了一倍。事实上，对于某些人群，如非常高龄的患者和继发性 AML 患者，这种方案可能与诱导化疗的完全缓解率相媲美，但尚需确立等效性。进一步的进展包括在诱导化疗中添加 gemtuzumab ozogamicin 和 FLT3 抑制剂，分别为核心结合因子和 FLT3 突变 AML 患者的生存带来改善。尽管如此，仍需要做大量工作来改善高危亚组患者的预后：虚弱的患者以及具有高危细胞遗传学和/或 TP53 突变的患者。有希望的是，AML 治疗的格局正在发生巨大变化，对于 AML，不再总是以强化治疗作为最佳答案。
