Addition of Selinexor to Standard Chemotherapy Disappoints in Phase II Trial

The addition of selinexor to standard intensive chemotherapy was not effective and even resulted in reduced treatment outcomes in patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS), prompting investigators to call the results “disappointing.”

The phase II study did, however, demonstrate the importance of minimal residual disease (MRD) status after two cycles of chemotherapy, the investigators noted.

The open-label, randomized study enrolled 102 patients aged 65 years and older (median age, 69 years; range, 65-80) years who were randomly assigned to standard chemotherapy (3+7) with or without oral selinexor 60 mg twice a week (both arms n=51) for days one to 24. In the second cycle, cytarabine 1,000 mg/m² twice daily one days one to six with or without selinexor was given.

Complete remission (CR)/CR with incomplete count recovery rates were higher in the control arm than in the investigational selinexor arm (80%; 95% CI, 69-91 versus 59%; 95% CI, 45-72; P=.018). At 18 months, event-free survival was 45% for the control arm versus 26% for the investigational arm (P=.012), and overall survival was 58% versus 33%, respectively (P=.009). MRD status after two cycles appeared to be correlated with survival, the authors added.

“The results of the current study are disappointing, with comparatively reduced overall and disease-free survival for the investigational selinexor treatment arm,” wrote the investigators, led by Jeroen JWM Janssen, MD, PhD, of the Department of the Hematology at the Amsterdam University Medical Centers.

Dr. Janssen and colleagues wrote that the poor results were largely due to lower anti-leukemic activity and deaths related to infection, and overall, the treatment had a negative impact on the patients’ outcomes.

“The addition of selinexor to standard chemotherapy does negatively affect the therapeutic outcome of elderly AML patients,” the authors concluded.

Janssen JJWM, Löwenberg B, Manz M, et al. Addition of the nuclear export inhibitor selinexor to standard intensive treatment for elderly patients with acute myeloid leukemia and high risk myelodysplastic syndrome. Leukemia. 2022. doi:10.1038/s41375-022-01657-3