Karyopharm reported mixed Phase 3 results from its Sentry trial of selinexor (Xpovio) plus ruxolitinib in front-line myelofibrosis and said it plans to meet the FDA about a potential supplemental NDA. The study met one of two co-primary endpoints with statistically significant improvement in spleen volume reduction of 35% or more. However, symptom outcomes measured by absolute total symptom score at week 24 were similar across arms, and the difference in symptoms between the selinexor+ruxolitinib and control arms did not reach statistical significance. Karyopharm characterized the overall survival signal as “promising,” which is likely to be central to its rationale for pursuing regulatory engagement. The development path now hinges on how the FDA evaluates endpoint hierarchy and what clinical risk-benefit evidence is considered most compelling. The readout continues to place selinexor’s repositioning in myelofibrosis against a crowded standard-of-care landscape dominated by JAK inhibition.