Rapid bone marrow blast reduction-guided selinexor-based regimen therapy in relapsed/refractory and newly diagnosed acute myeloid leukemia

作者：Yi Zhun Zhu, Shuai Su, Bin Xu, Shiyuan Zhang, Zhuoxin Wen, Xiwen Tong, Andie Fu, Jia Wei, Donghua Zhang · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-5223 · 研究领域：Acute Myeloid Leukemia Research、Retinoids in leukemia and cellular processes、Nuclear Structure and Function

Abstract Background:Therapeutic options for relapsed/refractory acute myeloid leukemia (R/R AML) remain limited, with poor long-term survival. Our observation of rapid blast decline kinetics in R/R AML patients treated with the selinexor-based regimen predicted therapeutic efficacy. We hypothesized that these kinetics could guide therapy intensification in AML. This prospective study evaluates the XAB regimen, leveraging blast-reduction patterns observed in R/R AML to optimize new diagnosed AML (ND AML) therapy. Methods:The single-arm prospective study was conducted at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. Patients aged 18-60years diagnosed with R/R or ND AMLwere included. All received the XAB regimen: selinexor (35 mg/m² twice weekly), azacitidine (75 mg/m²/day days 1–5), and venetoclax (100mg day 1, 200mg day 2, and 400 mg daily days 3- 21). Bone marrow assessments at weeks 1 and 2 were combined to classify blast reduction kinetics: Type A (sensitive): complete remission with/without count recovery (CR/CRi) at both timepoints; Type B (moderately sensitive): partial remission (PR) at week 1 → PR (blast continuously to decline)/CR/CRi at week 2; Type C (low sensitivity): PR/CR/CRi at week 1 → NR at week 2; Type D (resistant): NR at both timepoints. The Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (TJ-IRB20230955, TJ-IRB202502063) approved these prospective studies. ...