Data from the phase 3 SENTRY trial showed that adding selinexor (Xpovio) to ruxolitinib (Jakafi) significantly improved spleen responses in patients with JAK inhibitor-naive myelofibrosis. The study met one of its two co-primary endpoints, with 49.8% of patients receiving the combination achieving at least a 35% reduction in spleen volume at week 24, compared with 28.0% in the control arm. Although the trial did not meet its symptom-score endpoint, both groups experienced meaningful symptom improvement.
The combination produced rapid, deep, and durable spleen volume reductions and showed encouraging early survival trends, with lower mortality than the control arm. Molecular responses were also stronger, as reductions in disease-associated mutation burden correlated with higher spleen response rates.
Side effects were more frequent with selinexor, including thrombocytopenia, anemia, nausea, constipation, neutropenia, and fatigue. Long-term follow-up is ongoing to determine whether the early survival advantage translates into a lasting overall survival benefit.