即使存在新型靶向治疗，大多数急性髓系白血病 (AML) 患者也会发展为难治性/复发 (R/R) 疾病。考虑到该疾病的生物学复杂性和一线治疗的差异，只有针对 R/R AML 亚组的批准疗法，应优先考虑纳入临床试验。异基因造血细胞移植（HCT）是大多数患者唯一可能治愈的策略。由可测量残留病 (MRD) 的存在引发的治疗方法，包括同种异体 HCT，最近已发展到可预防明显的血液学复发。 HCT 之前经常进行化疗或靶向治疗的挽救治疗，以减少白血病负担。 Gilteritinib 已获得美国食品药品监督管理局 (FDA) 和欧洲药品管理局批准用于治疗复发性 FLT3 突变 AML 患者，而针对复发性 IDH1/2 突变 AML 的靶向治疗仅获得 FDA 批准。使用阿扎胞苷和维奈托克 (AZA/VEN) 后难治或复发的患者结局不佳。在这种情况下，即使可用的靶向治疗也无法获得令人满意的结果。正在进行的开发示例包括 menin 抑制剂、针对 NPM1 或 KMT2A 重排突变患者的靶向治疗、针对巨噬细胞免疫检查点 CD47 的抗体以及涉及 AZA/VEN 的三重组合。后者会引起显着的骨髓抑制作用，因此很难找到正确的时间表和剂量。版权所有 © 2023 美国血液学会。

The majority of patients with acute myeloid leukemia (AML) develops refractory/relapsed (R/R) disease even in the presence of novel and targeted therapies. Given the biological complexity of the disease and differences in front-line treatments, there are only approved therapies for subgroups of R/R AML and enrollment into clinical trials should be first priority. Allogeneic hematopoietic cell transplantation (HCT) is the only potentially curative strategy for the majority of patients. Therapeutic approaches, including allogeneic HCT, triggered by the presence of measurable residual disease (MRD) have recently evolved to prevent overt hematological relapse. Salvage therapy with chemotherapy or targeted therapy is frequently given prior to HCT to reduce the leukemic burden. Gilteritinib is approved by the Food and Drug Administration (FDA) and European Medicines Agency for patients with relapsed FLT3 mutated AML, while targeted therapy for relapsed IDH1/2 mutated AML has only FDA approval. Patients who are refractory or relapse after azacitidine and venetoclax (AZA/VEN) have a dismal outcome. In this setting, even available targeted therapies have unsatisfactory results. Examples of ongoing developments include menin inhibitors, a targeted therapy for patients with mutated NPM1 or KMT2A rearrangements, antibodies targeting the macrophage immune checkpoint CD47 as well as triple combinations involving AZA/VEN. The latter cause significant myelosuppressive effects, which make it challenging to find the right schedule and dose.Copyright © 2023 American Society of Hematology.