The Phase 3 SENTRY trial shows that adding selinexor (Xpovio) to ruxolitinib (Jakafi) improves outcomes for patients newly treated for myelofibrosis, especially in reducing spleen size.
At 24 weeks, 50% of patients receiving the combination therapy achieved at least a 35% reduction in spleen volume, compared with 28% of those taking ruxolitinib alone. However, the study did not meet its goal for symptom improvement, as both groups reported similar relief. Early survival data are still developing but suggest the combination may lower the risk of death by 57%.
Side effects were more frequent with the combination therapy. Patients commonly experienced low platelet counts, nausea, and low white blood cell counts. About 15% of patients stopped treatment due to side effects, compared with 9% in the ruxolitinib-only group.
Myelofibrosis treatment has long relied on JAK inhibitors like ruxolitinib. This study introduces a new approach by targeting the XPO1 protein, which is often overactive in cancer cells. Lead investigator John Mascarenhas said spleen reduction is an important goal because it is closely linked to improved survival.