Selinexor Plus Ruxolitinib Shrinks Spleens but Misses Its Symptom Goal in Phase 3 SENTRY, With an Early Survival Signal in Myelofibrosis

Overview

A Phase 3 trial of selinexor added to ruxolitinib in patients with myelofibrosis hit its spleen-shrinkage goal but missed its symptom goal, leaving the combination with a mixed primary result and an early, still-immature signal that it may extend survival. The SENTRY trial was presented as a late-breaking oral presentation at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting on June 2, 2026, with simultaneous publication in the Journal of Clinical Oncology, Karyopharm Therapeutics reported. The same data were subsequently reported at the European Hematology Association (EHA) 2026 Congress, according to the Menarini Group.

Myelofibrosis is a chronic blood cancer of the bone marrow that causes scarring, enlarged spleens, and debilitating symptoms. JAK inhibitors such as ruxolitinib have been the standard of care, but the SENTRY result tests whether layering a second mechanism on top of ruxolitinib can improve on it in patients who have not previously received a JAK inhibitor.

What We Know

SENTRY (also identified as XPORT-MF-034; NCT04562389) was a randomized, double-blind, placebo-controlled study that enrolled 353 patients and randomized them 2:1 to once-weekly selinexor at 60 mg plus ruxolitinib or to placebo plus ruxolitinib, per Karyopharm. The combination arm included 235 patients and the comparator arm 118, the Menarini Group reported. The trial enrolled patients who were JAK inhibitor-naïve with platelet counts above 100 × 10⁹/L, according to Karyopharm.

The study had two co-primary endpoints, and the result split between them: it met the first and missed the second, StockTitan reported.

On the first co-primary endpoint, spleen volume reduction of at least 35% (SVR35) at week 24, 49.8% of patients in the selinexor combination arm responded versus 28.0% in the ruxolitinib-alone arm, with an odds ratio of 2.58 (95% CI, 1.60 to 4.17; p<0.0001), Karyopharm reported. The spleen response held across timepoints: SVR35 was 49.4% versus 20.3% at week 12 and 46.9% versus 23.0% at week 36, according to the Menarini Group.

The second co-primary endpoint, the average change in absolute total symptom score (Abs-TSS) over 24 weeks, was not met, StockTitan reported. Symptom scores improved in both arms by a similar amount — a 9.9-point improvement at week 24 with the combination versus a 10.9-point improvement with ruxolitinib alone — according to the Menarini Group. The adjusted mean difference between arms was 0.97 points (95% CI, −1.07 to 3.02; p=0.825), Karyopharm reported.

The most closely watched figure was overall survival, a pre-specified secondary endpoint. The study showed a greater than 50% reduction in the risk of death for patients receiving the selinexor combination, with a hazard ratio of 0.43, the Menarini Group reported. As of February 20, 2026, 224 of 235 patients (95.3%) in the combination arm were alive versus 106 of 118 (89.8%) in the comparator arm; the hazard ratio of 0.43 carried a 95% confidence interval of 0.19 to 1.00 and a nominal one-sided p-value of 0.022, according to Karyopharm. The SENTRY results were published in the Journal of Clinical Oncology, per Karyopharm.

On safety, treatment-emergent adverse events occurred in 99.1% of the combination arm versus 97.4% of the ruxolitinib-alone arm, Karyopharm reported. The most common all-grade adverse events with the combination versus ruxolitinib alone included thrombocytopenia (59% vs 43%), nausea (57% vs 17%), and neutropenia (27% vs 9%); grade 3 or higher events occurred in 70% versus 50% of patients, while adverse events leading to death occurred in 0.9% versus 2.6% and confirmed leukemic transformation was 1.7% in each arm, according to Karyopharm. The Menarini Group said “no new safety signals were observed,” in its EHA report.

“The Phase 3 SENTRY results represent a meaningful advance for patients with myelofibrosis and underscore the promise of combining selinexor with ruxolitinib,” said Dr. John Mascarenhas, Professor of Medicine at the Icahn School of Medicine at Mount Sinai and Director of the Center of Excellence for Blood Cancers and Myeloid Disorders, in Karyopharm’s statement.

What We Don’t Know

The overall survival benefit is the headline most likely to drive interest, but it rests on immature data. The confidence interval around the 0.43 hazard ratio reaches up to 1.00, and the p-value reported was nominal and one-sided, per Karyopharm — meaning the survival result is suggestive rather than confirmatory and will need longer follow-up. The press materials did not state a regulatory filing date or approval pathway. Whether a missed symptom co-primary affects the regulatory reception of the combination is not addressed in the available materials.

Analysis

The central tension in SENTRY is that the combination clearly outperformed ruxolitinib on spleen shrinkage but added no measurable symptom benefit while increasing toxicity, particularly nausea and low blood counts. The companies are leaning on the survival signal and the link between spleen response and survival to make the case for the combination. “Achievement of spleen reduction is the essential goal of myelofibrosis treatment,” said Dr. Claire Harrison, Professor of Myeloproliferative Neoplasms and Deputy Chief Medical Officer at Guy’s and St. Thomas’ NHS Foundation Trust, in the Menarini report. Elcin Barker Ergun, CEO of the Menarini Group, said “the strength of the spleen response and the encouraging early overall survival data observed in the SENTRY study creates hope for a potential new treatment option for patients suffering from this devastating disease with dismal outcomes,” in the same report. With a missed symptom endpoint and survival data not yet mature, the durability of that case will depend on follow-up still to come.