In a phase I study, selinexor in combination with ruxolitinib demonstrated promising clinical activity with a manageable side effect profile in patients with treatment-naïve myelofibrosis (MF). The results of the trial were presented at the 2022 American Society of Hematology Annual Meeting.
The ongoing, multicenter, open-label, dose-escalation, phase I/II study is evaluating selinexor at doses of 40 mg and 60 mg orally once weekly plus ruxolitinib twice daily per standard of care in 28-day cycles. All patients received a 5-HT3 antagonist prior to each selinexor dose as needed for nausea prophylaxis.
Median patient age was 64 years (range, 44-77 years). Nine patients had primary MF, seven had post-essential thrombocythemia MF, and three had post-polycythemia vera MF. At baseline, two patients had packed red blood cell (RBC) transfusion-dependent anemia. Per the Dynamic International Prognostic Scoring System, six patients had intermediate-1 risk, nine had intermediate-2 risk, and four had high risk disease.
As of July 2022, 19 patients had received at least one dose of selinexor 40 mg (n=4) or 60 mg (n=15) and ruxolitinib.
Of the 14 patients evaluable for spleen response, 79% (n=11) achieved spleen volume reduction of ≥35% (SVR35) at week 12 (95% CI, 49-95); six of the seven (86%) evaluable patients achieved SVR35 at week 24 (95% CI, 42-100).
Most patients (86%; n=12) achieved SVR35 during the study. Thirteen patients with available data who received at least 12 weeks of treatment were evaluated for symptom response, nine (69%; 95% CI, 39-91) of whom had a total symptom score reduction of ≥50% by week 12.
Among the 17 patients with packed RBC transfusion-independence who received at least eight weeks of therapy, 11 (65%) maintained stable (±2g/dL) or improved (>2g/dL) hemoglobin levels at the last follow-up.
Among all 19 patients, the most common treatment-emergent adverse events were nausea (n=11; 58%), anemia (8; 42%), and vomiting (n=8; 42%). The most common grade 3 adverse events were thrombocytopenia and anemia; there were two grade 4 events, both of which were thrombocytopenia.
“In this preliminary analysis, the combination of selinexor and ruxolitinib shows promising clinical activity to date in patients with treatment-naïve MF,” the authors concluded.
Ali H, Kishtagari A, Maher K, et al. A phase 1, open-label, dose-escalation study of selinexor plus ruxolitinib in patients with treatment-naïve myelofibrosis. Abstract #1734. Presented at the 64th ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, Louisiana.