Selinexor Plus Ruxolitinib Demonstrates Improved Efficacy in Patients With Myelofibrosis
Key Takeaways:
- The SENTRY trial studied the impact of selinexor plus ruxolitinib on patients with myelofibrosis (MF) and found the regimen to achieve greater spleen volume reduction than treatment with ruxolitinib alone.
- Patients treated with selinexor plus ruxolitinib reported more high-grade adverse events (AEs), but the overall safety profile was manageable and consistent with prior studies.
- The study demonstrated the potential of selinexor plus ruxolitinib to improve outcomes and increase survival among patients with MF.
The Janus kinase (JAK) inhibitor ruxolitinib is the procedural treatment for MF. Although it improves symptoms and reduces splenomegaly, it is not associated with deep and durable responses.
The SENTRY Clinical Trial
Selinexor is an oral inhibitor of exportin 1 whose impact on MF is currently under review. In phase 1 of the SENTRY trial, selinexor plus ruxolitinib showed meaningful clinical activity.
The phase 3 segment of this trial compared the efficacy and safety of selinexor plus ruxolitinib with ruxolitinib alone in patients with JAK inhibitor–naïve MF.
Primary outcomes were spleen volume reduction ≥35% (SVR35) and absolute mean change in total symptom score (AbsTSS) from baseline to week 24.
In the study, 353 patients randomly received selinexor plus ruxolitinib (235) or placebo plus ruxolitinib (118).
After a follow-up of approximately 10 months, most patients continued with the study (81.3% in the selinexor plus ruxolitinib cohort and 83.1% in the ruxolitinib-only cohort). Reasons for discontinuation included patient withdrawal (11.1% and 2.5%), AEs (8.9% and 8.5%), physician decision (7.7% and 10.2%), and disease progression (6.0% and 10.2%).
Selinexor Plus Ruxolitinib Demonstrates Higher Efficacy
At week 24, 49.8% of patients in the selinexor plus ruxolitinib cohort achieved SVR35 while 28% of patients in the placebo plus ruxolitinib cohort achieved SVR35. Differences in spleen reductions were noticeable from week 12 through week 36.
While the AbsTSS end point was not met, both cohorts demonstrated improved symptom scores. At week 24, AbsTSS was −9.9 for selinexor plus ruxolitinib and −10.9 for ruxolitinib alone.
Selinexor Plus Ruxolitinib Displays Consistent Safety Profile
Safety was assessed among 234 patients in the selinexor plus ruxolitinib cohort and 116 patients in the ruxolitinib-only cohort.
AEs occurred among nearly all patients (99.1% vs 97.4%, respectively). AEs of grade 3 or higher occurred in 70.1% of patients in the selinexor plus ruxolitinib cohort and in 50% of patients in the placebo plus ruxolitinib cohort.
The most common AEs between both cohorts were anemia, thrombocytopenia, and neutropenia. Nausea was more common in the selinexor plus ruxolitinib cohort but was predominately low-grade.
Patients in the selinexor plus ruxolitinib cohort were more likely to receive modified doses or discontinue treatment entirely due to AEs.
Implications for Oncology Care
The study’s findings highlight the improved efficacy of selinexor plus ruxolitinib in treating patients with JAK inhibitor–naïve MF. Selinexor plus ruxolitinib demonstrated deeper and more durable responses compared to ruxolitinib alone, indicating it may be a promising first-line therapy option for MS.
The researchers said, “Notably, higher SVR35 rates were achieved despite a lower median relative dose intensity of ruxolitinib in the selinexor plus ruxolitinib group, as observed in the phase I portion, supporting an independent contribution of selinexor to efficacy and potential synergy.”
Reference
Bose P, Ali H, Al-Ali HK, et al. Selinexor plus ruxolitinib in Janus kinase inhibitor–naïve myelofibrosis: phase III SENTRY trial. J Clin Oncol. 2026;0:1-12. doi:10.1200/JCO-26-01080
