Reduced Spleen Volume Observed in Topline Selinexor/Ruxolitinib Trial Results

Topline results from the phase 3 SENTRY trial (NCT04562389) evaluating the combination of selinexor (Xpovio) plus ruxolitinib (Jakafi) demonstrated a reduction in spleen volume of 35% or more (SVR35) in patients with JAK inhibitor treatment-naïve myelofibrosis (MF) compared with ruxolitinib plus placebo, according to a news release from the manufacturer.^1,2

Among patients who received the combination of selinexor and ruxolitinib (n = 353), 50% achieved SVR35 at week 24 compared to 28% of patients who received ruxolitinib alone (P <.0001). The combination also achieved rapid spleen reduction, with 49% of patients in that arm already achieving SVR35 at week 12 compared with 20% who received ruxolitinib alone. This spleen volume reduction was sustained, as 47% of patients on the combination achieved SVR35 at week 36 compared with 23% who received ruxolitinib alone.

The mean change in absolute total symptom score (Abs-TSS) at week 24 relative to baseline was comparable across the two arms, with similar symptom improvement relative to baseline; the difference between the arms was not statistically significant. Patients who received the combination reported a 9.89 point improvement in Abs-TSS compared to a 10.86 point improvement in patients who received ruxolitinib alone.

SENTRY Trial Design and Additional Findings

In the SENTRY trial, eligible patients were randomly assigned 2:1 to receive treatment with either 60 mg oral once weekly selinexor plus ruxolitinib or placebo plus ruxolitinib administered in 28-day cycles on days 1, 8, 15, and 22. Ruxolitinib was administered twice daily continuously and dosed per label. Patients were stratified by DIPSS risk category (intermediate-1 vs intermediate-2 or high-risk), spleen volume (<1800 cm³ vs ≥1800 cm³), and baseline platelet counts (100 to 200 × 10⁹/L vs >200 × 10⁹/L). Treatment continued until progressive disease, intolerable toxicity, or until the patient met criteria for discontinuation of study treatment, death, or withdrawal of consent.

Additional topline results suggest an overall survival (OS) signal in patients in the treatment arm vs the control arm (HR, 0.43; 95% CI, 0.19-1.00; P = .0222). The manufacturer intends to continue to follow OS to maturity to further evaluate this signal.

Safety Profile

The five most common all-grade treatment emergent adverse events (TEAEs) in the selinexor plus ruxolitinib arm (n = 234) were thrombocytopenia (59% vs 43% in the placebo plus ruxolitinib arm, n = 116), anemia (57% vs 58%), nausea (57% vs 17%), constipation (32% vs 36%), and neutropenia (27% vs 9%). The rate of grade 3 or higher TEAEs was 70% in the selinexor plus ruxolitinib arm compared to 50% in the placebo plus ruxolitinib arm. The rate of TEAEs leading to treatment discontinuation was 15% in the selinexor plus ruxolitinib arm and 9% in the placebo plus ruxolitinib arm. The rate of confirmed leukemic transformations was the same across both arms of the trial at 1.7%.

“The results from SENTRY are an important development for patients as the combination of selinexor plus ruxolitinib meaningfully improved spleen response and we observed a promising signal in overall survival. Reducing spleen volume remains one of the most important treatment goals in myelofibrosis since achieving SVR35 is associated with improvement in overall survival,” John Mascarenhas, MD, said in a release. Mascarenhas is professor of medicine at the Icahn School of Medicine at Mount Sinai and director, Center of Excellence for Blood Cancers and Myeloid Disorders, .

“While the symptom end point did not reach statistical significance, patients treated in both arms achieved similar symptom improvement relative to baseline. Importantly, while JAK inhibitors have been the backbone of therapy, continued progress requires new therapies that target additional biological pathways. Inhibition of XPO1 represents a differentiated mechanism that has the potential to address these pathways and evolve treatment beyond JAK inhibition alone,” Mascarenhas said.

“Selinexor's differentiated mechanism provides a complementary approach to JAK inhibition and highlights the importance of targeting additional biological pathways beyond JAK signaling to further advance outcomes for patients with myelofibrosis. I am encouraged by the speed and magnitude of spleen response, and the promising overall survival signal and evidence of potential disease modification. In totality, these data underscore selinexor's potential to meaningfully improve clinical outcomes for patients with myelofibrosis,” Reshma Rangwala, MD, PhD, chief medical officer and head of research of Karyopharm, said in a release.

REFERENCES

1. Karyopharm's Phase 3 SENTRY Trial in Myelofibrosis Met First Co-Primary Endpoint, Demonstrating Statistically Significant Improvement in Spleen Volume Reduction. News release. March 24, 2026. Accessed March 24, 2026. https://tinyurl.com/mry96wp8

2. Mascarenhas J, Maher K, Rampal R, et al. Selinexor plus ruxolitinib in JAK inhibitor treatment-naïve myelofibrosis: SENTRY Phase 3 study design. Future Oncol. 2025;21(7):807-813. doi:10.1080/14796694.2025.2461393