In the registrational SENTRY Phase 3, the combination produced a 49.8% vs 28% spleen volume response at 24 weeks, statistically significant, but the second main goal measuring symptom relief has not yet been reported.
Myelofibrosis is a rare, chronic blood cancer that scars the bone marrow and often pushes the spleen into painful overgrowth, while sapping patients with fatigue, night sweats, and weight loss. For years, the standard first-line therapy has been the JAK inhibitor ruxolitinib, a pill that shrinks the spleen and eases symptoms for many patients but loses its grip over time. A new registrational Phase 3 trial reported at the European Hematology Association (EHA) 2026 congress now offers one piece of evidence that the standard can be improved at the front line, and one piece that the field still has to wait for.
The SENTRY trial, run by Menarini Group's wholly-owned subsidiary Stemline Therapeutics in collaboration with Karyopharm Therapeutics, randomized 353 patients with myelofibrosis to receive either selinexor, a once-weekly oral inhibitor of the nuclear-export protein XPO1, or placebo, on top of ruxolitinib. The first co-primary endpoint was spleen volume reduction of at least 35% (SVR35) at week 24. According to the Menarini / Stemline press release distributed via PR Newswire on 14 June 2026, 49.8% of patients in the 235-patient selinexor-plus-ruxolitinib arm reached SVR35, versus 28.0% in the control arm. The result is statistically significant, and the EHA scientific committee selected the data for a late-breaking oral presentation, the kind of slot reserved for findings the program committee considers important enough to anchor a congress session.
The second co-primary endpoint, the absolute change in total symptom score (Abs-TSS) at 24 weeks, has not yet been reported. In pivotal myelofibrosis trials, hitting SVR35 alone does not constitute full success. A win on the symptom endpoint would let the combination match the profile of approved ruxolitinib-based regimens; a miss would leave clinicians with a spleen benefit and a question about whether patients feel meaningfully better. Until that number lands, SENTRY is half a win, with the second half the open question.
The release also leans on a post-hoc analysis suggesting that SVR35 may predict overall survival in myelofibrosis, a claim that has not been pre-specified and should be treated as hypothesis-generating rather than confirmatory. Survival benefits are notoriously hard to demonstrate in a chronic, slow-progressing disease measured over months, and the field will want a pre-specified survival analysis or a longer follow-up before reading the post-hoc as a survival win.
Selinexor's existing label, set in multiple myeloma and diffuse large B-cell lymphoma, carries a class-level set of side effects that any add-on to chronic ruxolitinib will need to absorb: low platelets, low neutrophils, gastrointestinal toxicity, fatigue, and low sodium. The SENTRY release is silent on whether those issues were worse on the combination than on ruxolitinib alone. The tolerability readout, expected in the EHA late-breaker, will be a critical part of the picture for any clinician deciding whether to escalate first-line therapy in a patient who is responding to ruxolitinib but still symptomatic.
For now, the practical map is this: SENTRY has produced a real, statistically clear SVR35 win for selinexor on top of ruxolitinib in first-line myelofibrosis, and a regulatory filing in this indication is now on the table. It has not yet shown that patients feel better, and it has not yet shown that the spleen benefit translates into a survival benefit. The next SENTRY readout, the EHA late-breaking oral itself, and any subsequent peer-reviewed publication will determine whether the combination becomes a routine first-line option or a more selective choice for patients in whom spleen burden, not symptoms, drives the treatment decision.