Karyopharm's Selinexor Hits Spleen Endpoint but Misses on Symptoms in Myelofibrosis
By FieldPulse Editorial · March 26, 2026
Tags: Pipeline, Hematology, Oncology
Karyopharm's Phase 3 SENTRY trial in myelofibrosis met its spleen volume co-primary endpoint (50% vs 28%) but missed the symptom reduction co-primary. The company plans to meet with the FDA.
Karyopharm Therapeutics reported mixed results from the Phase 3 SENTRY trial of selinexor (marketed as Xpovio in multiple myeloma) in myelofibrosis — hitting one co-primary endpoint convincingly while missing the other entirely.
The split outcome creates a complicated regulatory and commercial picture that the company will now need to navigate with the FDA.
The SENTRY trial evaluated selinexor in combination with Incyte's ruxolitinib (Jakafi) versus placebo plus ruxolitinib in patients with myelofibrosis who had a suboptimal response to ruxolitinib alone.
The two co-primary endpoints were spleen volume reduction of 35% or more (SVR35) at week 24, and a 50% or greater reduction in total symptom score (TSS50) at the same time point.
The Data: One Win, One Miss On the spleen endpoint , selinexor plus ruxolitinib delivered a clear victory: 50% of patients achieved SVR35 compared to 28% on placebo plus ruxolitinib (p On the symptom endpoint , however, the combination failed to show a statistically significant improvement in TSS50 over the control arm.
Symptom burden in myelofibrosis — which includes fatigue, night sweats, bone pain, and early satiety — is a critical component of the disease experience, and regulators have increasingly emphasized patient-reported outcomes alongside objective measures like spleen volume.
The disconnect between spleen reduction and symptom improvement is not uncommon in myelofibrosis, but it creates a problem for a trial designed with two co-primary endpoints.
In many trial designs, both co-primary endpoints must be met for the study to be considered a success.
Whether the FDA will view the spleen data as sufficient to support approval — potentially with a narrower label — is the central regulatory question that Karyopharm will need to address.
The Regulatory Path Forward Karyopharm has announced plans to meet with the FDA to discuss the SENTRY results and determine the path forward.
Several scenarios are possible: Scenario 1: Approval base.