Selinexor-based non-intensive chemotherapy regimens adjusted according to early responses achieve high early remission in newly diagnosed AML or MDS Free

Background Some newly diagnosed (ND) acute myeloid leukemia (AML) or higher-risk myelodysplastic syndrome (MDS) patients (pts) are ineligible for or unwilling to receive intensive chemotherapy. These pts usually receive low-intensity regimens. preliminary data from clinical trials have indicated that non-intensive chemotherapy containing selinexor can achieve a relatively high response rate in unfit AML. Therefore, we explored selinexor-based chemotherapy-free or low-dose chemotherapy regimens in the above-mentioned ND AML or MDS.

Aims To investigate the efficacy and safety of selinexor based non-intensive chemotherapy for the ND AML or MDS, and evaluate the timing for early adjustment of the regimens.

Methods Pts who refused or were ineligible for intensive chemotherapy were enrolled and received the following regimens: selinexor was initially dosed at 35 mg/m² twice a week (60mg BIW). Azacitidine 75 mg/m²/d for 5 to 7 days, venetoclax was administered at 100 mg, 200 mg, and 400 mg on d1-3, respectively, followed by 400 mg daily days 3 to 14 (XAB regimen).

Bone marrow puncture was performed every week during the treatment. According to whether CR/CRi was achieved in the first and second weeks, subsequent treatments were adjusted according to the response. Pts who achieved CR/CRi early subsequently received allo-HSCT if they were fit for or willing to undergo transplantation. Other pts were treated with low-dose cytarabine (Ara-C) 50mg/d on the basis of XAB regimen for 5 days, followed consolidation and maintenance therapy. The specific treatment process can be found in flow chart figure.

Results As of July 2025, 29 pts were enrolled, median age of 58, comprising 17 males. 18 pts with AML, 11 pts with MDS. Risk stratification was as follows: AML: 5 adverse, 6 intermediate, 1 favor, 6 unknown (owing to the absence of available mutation or chromosomal information); MDS: 1 very high, 5 high, 3 intermediate, 2 unknown.

After one week of XAB treatment, 17 pts (58.6%) achieved CR/CRi, 4 (13.7%) PR, and 8 (27.5%) NR. After the second week of treatment, 20 pts (68.9%) CR, 7 (24.1%) PR, 2 (6.8%) NR (3 of NR and 3 of PR acquired CR/CRi respectively, and 4 of NR acquired PR). Five pts subsequently received allo-HSCT. The median follow-up time was 60 days, and 22 pts (75.9%) were survived.

In the most recent 14 pts enrolled, we adjusted the frequency of selinexor in the XAB regimen from BIW to three times a week (60mg TIW). We found that this could enable the bone marrow blasts≤5% more rapidly (64.3% of pts in the first week and 71.4% in the second week), while in the BIW group were 53.3% and 66.7% respectively.

After 2 weeks of treatment, among pts evaluable for safety, the incidence of grade 4 neutropenia was 80.0% (12/15) in BIW group, with a median recovery time of 13 (range, 0 to 20) days. In TIW group, the incidence was 92.8% (13/15), and the median recovery time was 8 (range, 1 to 41) days. The incidence of grade 4 thrombocytopenia was 40% (6/15) in BIW group, with a median recovery time of 1 (range, 0 to 16) days. In TIW group, the incidence was 57.1% (8/15), and the median recovery time was 1 (range, 0 to 25) days.

Conclusion A high rate of early remission could be achieved in ND AML/MDS pts treated with non-intensive regimen containing Selinexor, and administration of selinexor TIW achieves a higher rate of early remission compared with BIW. Selinexor-containing regimens provide a new treatment option for these pts.