Selinexor Plus Ruxolitinib in Janus Kinase Inhibitor-Naïve Myelofibrosis: Phase III SENTRY Trial

Area of Science:

• Hematology
• Oncology
• Clinical Trials

Background:

• Myelofibrosis is a serious bone marrow disorder.
• Ruxolitinib is a standard treatment but doesn't always eliminate the disease.
• Selinexor shows promise in treating myelofibrosis.

Purpose of the Study:

• To evaluate the efficacy and safety of selinexor plus ruxolitinib versus ruxolitinib alone in JAK inhibitor-naïve myelofibrosis patients.
• To assess spleen volume reduction and symptom score changes as primary endpoints.

Main Methods:

• A double-blind, randomized, placebo-controlled, phase 3 trial.
• 353 JAK inhibitor-naïve myelofibrosis patients were randomized (2:1) to selinexor plus ruxolitinib or placebo plus ruxolitinib.
• Co-primary endpoints: spleen volume reduction ≥35% (SVR35) and absolute mean change in total symptom score (AbsTSS) at Week 24.

Main Results:

• SVR35 was achieved by 49.8% in the selinexor group vs. 28.0% in the placebo group (P<0.0001).
• The AbsTSS co-primary endpoint was not met; symptom scores improved similarly in both groups.
• Median follow-up of ~12 months showed a hazard ratio for overall survival of 0.43 (P=0.022).
• Grade ≥3 adverse events were more common with selinexor (70.1% vs. 50.0%), primarily anemia, thrombocytopenia, and neutropenia.

Conclusions:

• Selinexor plus ruxolitinib met the SVR35 co-primary endpoint in myelofibrosis but not the symptom score endpoint.
• An early overall survival difference favoring the combination was observed.
• The safety profile was consistent with known side effects of individual agents.