Division of Hematology and Medical Oncology, West Virginia University Cancer Institute, Wheeling Hospital, Wheeling, WV, USA.
Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
Leuk Lymphoma. 2023 Dec;64(13):2091-2100. doi: 10.1080/10428194.2023.2253480. Epub 2023 Sep 4.
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/m), the maximum tolerated dose was 30 mg/m. 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.
Selinexor 是一种核输出蛋白 Exportin-1 的口服抑制剂，在复发/难治性（R/R）急性髓系白血病（AML）的临床试验中表现出单药活性的潜力，并且与拓扑异构酶（topo）IIα 抑制剂具有临床前协同作用。我们在 23 名年龄 < 60 岁的 R/R AML 患者中进行了 selinexor 联合米托蒽醌、依托泊苷和阿糖胞苷（MEC）的 1 期剂量递增研究。由于 2 名患者在剂量水平 2（selinexor 40mg/m）出现剂量限制的低钠血症，最大耐受剂量为 30mg/m。最常见的≥3 级治疗相关非血液学毒性是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。总缓解率为 43%，6 名患者（26%）达到完全缓解（CR），2 名（9%）达到不完全血细胞计数恢复的 CR，2 名（9%）达到形态学无白血病状态。10 名应答者中有 7 名接受了异基因造血干细胞移植。Selinexor 联合 MEC 是治疗 R/R AML 患者的一种可行的治疗选择。
