Selinexor and Ruxolitinib Combination Reduces Spleen Volume in Myelofibrosis SENTRY Trial

A combination of selinexor and ruxolitinib significantly reduced spleen volume in patients with first-line myelofibrosis, according to data from the SENTRY phase 3 trial presented June 14, 2026. The Menarini Group and Stemline Therapeutics reported a 49.8% response rate compared to 28% for ruxolitinib alone at week 24.

The SENTRY trial (NCT04562389) involved 353 patients. Researchers compared 60 mg of selinexor combined with ruxolitinib against ruxolitinib monotherapy. The study aimed to meet two primary goals: a 35% or greater reduction in spleen volume (SVR35) and an improvement in the absolute total symptom score (Abs-TSS).

How did the combination therapy perform against the control?

The combination therapy met its first primary endpoint. At week 24, 49.8% of patients receiving selinexor and ruxolitinib achieved SVR35, while only 28% of the control group reached that mark. This trend appeared early, with a 49.4% response rate for the combination group at week 12 compared to 20.3% for the placebo and ruxolitinib group.

The trial did not meet its second primary endpoint regarding symptom scores. Patients using the combination saw a 9.9-point improvement in Abs-TSS at week 24. This was comparable to the 10.9-point improvement seen in patients receiving ruxolitinib alone, a difference the companies stated was not statistically significant.

Did You Know? Myelofibrosis is a rare blood cancer affecting approximately one to two people per 100,000 individuals annually, with a median survival rate of six years following diagnosis.

Why are these results significant for cancer patients?

Spleen reduction is a primary goal in treating myelofibrosis, a condition where abnormal blood-forming cells cause scarring in the bone marrow. Dr. Claire Harrison, a professor of myeloproliferative neoplasms at Guy’s and St. Thomas’ NHS Foundation Trust, stated the SENTRY results were “rapid, profound and durable.”

Early data suggests a possible impact on survival. While the data remains immature, the study showed a hazard ratio of 0.43 for overall survival. According to the report, this represents a reduction in the risk of death of more than 50% for patients receiving the selinexor combination compared to those on ruxolitinib alone.

Expert Insight: Samantha Carter notes that while the failure to significantly outperform ruxolitinib in symptom scores is a limitation, the deep spleen response and the early survival signal may shift the clinical priority toward disease modification rather than just symptom management.

What may happen next for this treatment?

The Menarini Group and Stemline Therapeutics presented these findings as a late-breaking oral presentation at the 2026 European Hematology Association (EHA) Congress. The companies may use this data to seek further regulatory approvals for the combination therapy.

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Future analysis may focus on the variant allele frequency (VAF) reduction. At week 24, 32% of the combination group saw a VAF reduction compared to 23.9% in the ruxolitinib group. This suggests the combination could potentially modify the course of the disease.

Comparative Trial Results at Week 24

SVR35 (Spleen Reduction): 49.8% (Combination) vs. 28.0% (Control)
Abs-TSS (Symptom Improvement): 9.9 points (Combination) vs. 10.9 points (Control)
VAF Reduction: 32% (Combination) vs. 23.9% (Control)

Frequently Asked Questions

What is SVR35 in the context of this study?

SVR35 refers to a reduction in spleen volume of 35% or more, which is a primary goal for treating patients with myelofibrosis.

Did the combination therapy improve symptoms more than the single drug?

No. The combination therapy showed a 9.9-point improvement in symptoms, which was not statistically significantly different from the 10.9-point improvement seen with ruxolitinib alone.

What was the impact on the risk of death?

Early, immature data indicated a reduction in the risk of death of over 50% for the combination group, with a hazard ratio of 0.43.

How do you think the balance between symptom relief and survival rates should influence new cancer treatment approvals?