Selinexor是核传送蛋白Exportin-1的口服抑制剂，在复发/难治性急性髓系白血病（AML）临床试验中显示出良好的单药活性，并与拓扑异构酶（topo）IIα抑制剂表现出协同作用。我们进行了一项1期递增剂量研究，使用selinexor与米托甲酮、依托泊苷和阿糖胞苷（MEC）治疗23名< 60岁复发/难治性AML患者。由于第2剂量水平（selinexor 40 mg/m2）中2名患者出现限制剂型低钠血症，最大耐受剂量为30 mg/m2。最常见的≥3级与治疗相关的非血液学毒性为发热性中性粒细胞减少症、导管相关感染、腹泻、低钠血症和败血症。总体反应率为43%，6名患者（26%）达到完全缓解（CR），2名患者（9%）CR伴不完全计数恢复，2名患者（9%）达到形态学白血病无病状态。十名反应者中有7名进行异基因干细胞移植。selinexor与MEC的组合是一种可行的复发/难治性AML患者治疗选择。

Selinexor, an oral inhibitor of the nuclear transport protein Exportin-1, shows promising single-agent activity in clinical trials of relapsed/refractory (R/R) acute myeloid leukemia (AML) and preclinical synergy with topoisomerase (topo) IIα inhibitors. We conducted a phase 1, dose-escalation study of selinexor with mitoxantrone, etoposide, and cytarabine (MEC) in 23 patients aged < 60 years with R/R AML. Due to dose-limiting hyponatremia in 2 patients on dose level 2 (selinexor 40 mg/m2), the maximum tolerated dose was 30 mg/m2. The most common grade ≥ 3 treatment-related non-hematologic toxicities were febrile neutropenia, catheter-related infections, diarrhea, hyponatremia, and sepsis. The overall response rate was 43% with 6 patients (26%) achieving complete remission (CR), 2 (9%) with CR with incomplete count recovery, and 2 (9%) with a morphologic leukemia-free state. Seven of 10 responders proceeded to allogeneic stem cell transplantation. The combination of selinexor with MEC is a feasibile treatment option for patients with R/R AML.