Department of Hematology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
Future Oncol. 2021 Mar;17(7):837-851. doi: 10.2217/fon-2020-0615. Epub 2021 Feb 1.
Older acute myeloid leukemia patients usually experience a bleak outcome, especially those in the unfit group. For this unfit category, intensive chemotherapy and allogeneic stem cell transplantation are usually accompanied by higher early mortality, which results from higher risk genetic profiles and worse psychological and physiological conditions. The significant improvement in genetic technology recently has driven the appearance of several mutation-targeted therapies, such as FLT3, Bcl-2, IDH and Hedgehog pathway inhibitors and an anti-CD33 antibody-drug conjugate, which have changed enormously the therapeutic landscape of acute myeloid leukemia. This review describes the treatment dilemma of the unfit group and discusses the objective clinical data of each targeted drug and mechanisms of resistance, with a focus on combination strategies with fewer toxicities and abrogation of drug resistance.
老年急性髓系白血病患者通常预后较差，尤其是身体状况不佳的患者。对于这类不适合接受高强度治疗的患者，强化化疗和异基因造血干细胞移植通常伴随着更高的早期死亡率，这是由于高风险的遗传特征以及更差的心理和生理状况所致。最近基因技术的显著进步推动了几种突变靶向治疗药物的出现，如 FLT3、Bcl-2、IDH 和 Hedgehog 通路抑制剂以及一种抗 CD33 抗体药物偶联物，这些药物极大地改变了急性髓系白血病的治疗格局。本综述描述了身体状况不佳患者的治疗困境，并讨论了每种靶向药物的客观临床数据和耐药机制，重点关注毒性更小和克服耐药性的联合治疗策略。
