Prognostic and Therapeutic Implications of Early Assessment in AML and MDS Patients Treated with Selinexor-Containing Chemotherapy-Free Regimen
Authors: Shuai Su , Xu Bin , Tong Xiwen , Zhu Yi , Zhang Shiyuan , Mao Xia , Wang Zhiqiong , Xiao Min , Zhang Donghua , Wei Jia 
Published: December 2024

Background:
There is no consensus on treatment strategies for relapsed or refractory acute myeloid leukemia (R/R AML) and myelodysplastic syndrome (MDS). Non-chemotherapy strategies such as the “XAB” regimen, which combines selinexor, an inhibitor of exportin-1 (XPO1), with azacitidine (A) and venetoclax, a BCL-2 inhibitor (B), are currently widely studied. However, considerable heterogeneity among patients results in varying treatment efficacy. Our study aimed to explore the application of early assessment in AML and MDS patients receiving the XAB regimen.
Methods:
This study was conducted at Tongji Hospital. Patients aged 18-70 years diagnosed with AML and MDS were included. The specific XAB regimen consisted of selinexor 35mg/m2 twice weekly for two consecutive weeks, azacitidine 75mg/m2/d on days 1-5, and venetoclax 100mg on day 1, 200mg on day 2, followed by 400mg daily. Patients underwent bone marrow (BM) examinations on days 7 and 14. Based on BM examination on day 7, patients were categorized into early response (≥50% decrease in BM blast percentage compared to baseline), early minimal response (&lt;50% decrease), and early non-response (no change or increase). If the patient exhibits an early response, the current course of treatment will continue. In cases of early minimal response, 50mg per day of cytarabine will be added for 5 days. For patients showing early non-response, the current treatment will stop. Patients who did not achieve complete remission (CR)/CR with incomplete hematologic recovery (CRi) but partial remission (PR) after the initial course will receive an additional cycle of treatment. Patients achieving CR/CRi can subsequently undergo hematopoietic stem cell transplantation (HSCT) or receive consolidation and maintenance therapy based on the XAB regimen, while those with persistent non-remission (NR) will stop the XAB regimen and receive alternative therapy.
Results:
As of July 22, 2024, 23 patients receiving the XAB regimen enrolled. Baseline characteristics included: median age of 51; Male: Female =13:8; R/R AML and MDS incidences were 14 and 1, respectively, while newly diagnosed AML and MDS were 6 and 2, respectively. Of the 23 patients, 18 showed an early response, 4 early minimal response, and 1 early non-response. After one course of treatment, 13 (56.5%) patients achieved CR/CRi, and 3 patients achieved PR, 2 of whom received another cycle of the XAB regimen, resulting in 1 patient achieving CR. Additionally, 7 patients were NR. Based on changes in BM blast percentage on days 7 and 14, patients were classified into four groups: (1) early decrease to ≤5% with no subsequent increase. (2) gradual early decrease &gt;5% with continued decrease. (3) early decrease followed by increase. (4) early increase. Among the 23 patients, 10 belonged to Group 1, all achieving CR/CRi. By the end of follow-up, 1 patient died from severe infection. 6 patients belonged to Group 2, of whom 3 achieved CR/CRi, 1 died from disease progression, and 2 died from transplant-related complications. 6 patients belonged to Group 3, of whom 2 died from disease progression. 1 patient belonged to Group 4, who died from disease progression. None of the patients in Group 3 and Group 4 achieved CR/CRi. Patients in Group 1 showed the best response to the XAB regimen, indicating potential for subsequent HSCT or consolidation and maintenance therapy based on the XAB regimen. Patients who did not achieve early CR/CRi showed a gradual decrease in BM blast percentage (Group 2), even achieving CR eventually, while other patients experienced subsequent elevation of BM blast percentage (Group 3), indicating resistance to the XAB regimen. For these patients in Group 2 and Group 3, an early comprehensive evaluation system is imperative to establish, incorporating methods such as minimal residual disease detection and risk stratification to evaluate and intervene promptly, thereby improving prognosis. Patients with an early increase in BM blast percentage (Group 4) showed poor response to the XAB regimen and should be promptly discontinued for alternative therapies.
Conclusion:
Early assessment has predictive value for efficacy and prognosis in patients who received an XAB regimen, helping us make prompt decisions to select the most effective treatment for patients.