Selinexor added to standard myelofibrosis therapy shrank enlarged spleens in 49.8% of patients versus 28% on standard care, but the phase 3 SENTRY trial missed its second main goal: a patient reported symptom score.
Myelofibrosis is a rare, chronic blood cancer in which scar tissue builds up inside the bone marrow and crowds out normal blood cell production. The most visible sign is an enlarged spleen, the organ that steps in to do the marrow's job. Patients often feel full after small meals, lose weight, and carry chronic fatigue and abdominal discomfort. Ruxolitinib, a JAK inhibitor pill that calms the inflammatory signaling driving the disease, has been the default first-line treatment for more than a decade. Its ceiling is well known: most patients see some spleen shrinkage, but the response is rarely durable, and the disease typically progresses.
A late-breaking presentation at the European Hematology Association (EHA) 2026 Congress in Florence on Monday reported the first phase 3 data testing whether adding a second drug, selinexor, to ruxolitinib can push past that ceiling. Selinexor blocks a nuclear-export protein called XPO1, which cancer cells rely on to keep tumor-suppressor proteins out of the nucleus. It is already approved for multiple myeloma and for a separate myelofibrosis indication. The SENTRY trial enrolled 353 patients with myelofibrosis who had never taken a JAK inhibitor, randomizing 235 to selinexor plus ruxolitinib and 118 to placebo plus ruxolitinib, according to the Menarini Group and Stemline Therapeutics press release distributed via PR Newswire.
SENTRY set itself two co-primary goals, meaning the trial needed to clear both to claim a full success. The first was a 35% or greater reduction in spleen volume, a measurement captured by CT or MRI and tracked as a percentage change from baseline. The combination won that comparison clearly: 49.8% of patients on selinexor plus ruxolitinib hit that threshold at 24 weeks, compared with 28% on placebo plus ruxolitinib, according to the sponsor's release. At 12 weeks the split was 49.4% versus 20.3%, and at 36 weeks it was 46.9% versus 23%.
The second co-primary goal measured something different: how patients actually feel. The Absolute Total Symptom Score, or Abs-TSS, is a patient-reported scale that quantifies the night sweats, itching, abdominal discomfort, early satiety, and fatigue that define the lived experience of myelofibrosis. On that endpoint, the combination did not beat placebo. Mean change from baseline at 24 weeks was −9.9 points for the selinexor arm and −10.9 points for the control arm, a difference the sponsor's analysis described as not statistically significant, per the press release.
That single miss matters because regulators and clinical guidelines have, in recent years, signaled that patient-reported outcomes are not an afterthought. A drug that shrinks the spleen but does not move the symptom needle is a more difficult sell, particularly when selinexor's known side effects, including nausea, fatigue, and low blood counts, would have to be weighed against an anatomy-only win.
The data do offer a more intriguing signal, but it comes with a critical asterisk. The press release reports a preliminary overall-survival hazard ratio of 0.43, which would mean a more than 50% reduction in the risk of death for the combination arm, according to the sponsor. The release labels that finding preliminary. Overall survival was a prespecified secondary endpoint, but the trial was not powered to detect it. The supporting analysis the sponsor highlights is a post-hoc look at whether a 35% spleen-volume reduction itself predicts survival, paired with a separate phase 1 dataset, per the release. Post-hoc, hypothesis-generating analyses are useful for shaping the next study. They are not evidence of a survival benefit in the current one.
A third exploratory endpoint looked at variant allele frequency, a blood-based measure of how much of the malignant cell clone remains. Mean reduction at 24 weeks was 32% in the combination arm versus 23.9% in the control arm, according to the press release. The release frames that as a possible disease-modifying signal, a phrase clinicians use cautiously because it implies the underlying disease biology is being altered, not just its symptoms. That language is the sponsor's framing, not a regulatory conclusion.
The trial's identity and sponsorship are independently documented. SENTRY is registered on ClinicalTrials.gov as NCT04562389, sponsored by Karyopharm Therapeutics with commercial partner the Menarini Group through its Stemline subsidiary. The EHA 2026 abstract record for the late-breaking oral names Prof. Claire Harrison of Guy's and St. Thomas' NHS Foundation Trust as the presenting investigator.
What the data do not contain is any claim of regulatory submission, approval, label change, pricing, or patient access in any market. The press release is a snapshot of the sponsor's analysis, not a regulator's verdict. The next test is the full EHA late-breaking oral this week in Florence and any subsequent peer-reviewed publication. For clinicians weighing a treatment decision, the practical question is whether a 21.8-percentage-point improvement in spleen response, durable out to 36 weeks, justifies adding a second drug with its own toxicity profile when the patient-facing symptom score did not move and the survival signal remains preliminary. That question is not answered by the press release.