Selinexor yields responses in patients with myelodysplastic syndromes (MDS) or oligoblastic acute myeloid leukemia (AML) refractory to hypomethylating agents, with manageable adverse events, according to the results of a study published in The Lancet Haematology.

The single-center, single-arm, phase 2 trial ( Identifier: NCT02228525) conducted at the Memorial Sloan Kettering Cancer Center in New York, NY, aimed to assess the safety and activity of selinexor, a selective inhibitor of nuclear export, in adult patients with MDS or oligoblastic AML refractory to hypomethylating agents, a population with a median overall survival of less than 6 months.

Patients were enrolled in the study between September 23, 2014, and March 13, 2018; participants received 3-week cycles of oral selinexor, 60 mg twice a week for 2 weeks, followed by 1 week off to improve tolerability. The primary outcome was overall response rate, and secondary outcomes included the frequency of stable disease, safety, and overall survival.

Continue Reading

The median follow-up duration was 8.5 months (interquartile range [IQR], 3.1-12.2 months). Of 25 enrolled patients (median age, 77 years; IQR, 70-81 years), only those who received selinexor and completed at least 1 posttreatment disease assessment were evaluable for activity assessment (23 patients).  

The trial met its primary endpoint with 6 of 23 patients achieving marrow complete response, an overall response rate of 26% (95% CI, 10-48), and 12 patients (52%; 95% CI, 31-73) achieved stable disease. Among the evaluable patients, the median overall survival was 8.7 months, and the 1-year probability of survival was 30%.

An exploratory analysis of whole transcriptome sequencing of pretreatment and posttreatment bone marrow specimens revealed that exportin 1 (XPO1) inhibition was associated with altered splicing. Furthermore, patients with spliceosomal mutations were more likely to respond to selinexor therapy.

All 25 patients who received selinexor were included in the safety analysis. The most common grade 3 or 4 adverse events (AEs) were thrombocytopenia (32%; 8/25) and hyponatremia (20%; 5/25). No drug-related serious AEs occurred, and the investigators concluded that AEs were manageable with supportive care.

“This phase 2 study of the single agent selinexor in patients with [MDS] refractory to hypomethylating agents met the primary endpoint of overall response rate and was tolerable after an [optimized] dosing regimen,” wrote the authors.

“We therefore propose that further development of XPO1 inhibitors for [MDS] is warranted and recommend including more patients with splicing factor mutations in future trials to confirm this genotype as a predictor of response,” the investigators noted.

The authors acknowledged the small sample sizes in the study and suggested that the subgroup analyses in particular should be interpreted with caution. In addition to its potential use as monotherapy, the authors also suggested that selinexor could be used in combination therapies in MDS and conclude that additional studies are needed.

Disclosures: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Taylor J, Mi X, Penson A V, et al. Safety and activity of selinexor in patients with myelodysplastic syndromes or oligoblastic acute myeloid leukaemia refractory to hypomethylating agents: a single-centre, single-arm, phase 2 trial. Lancet Haematol. 2020;7(8):e566-e574. doi:10.1016/S2352-3026(20)30209-X