Karyopharm Therapeutics (KPTI) Study result summary

Study design and objectives

• Phase III SENTRY trial evaluated selinexor plus ruxolitinib versus ruxolitinib alone in JAK inhibitor-naïve myelofibrosis patients (N=353), randomized 2:1, stratified by risk, spleen volume, and platelet counts.

• Co-primary endpoints were spleen volume reduction (SVR35) and total symptom score (TSS) at week 24; secondary endpoints included overall survival, VAF reduction, hemoglobin stabilization, and bone marrow fibrosis improvement.

• The combination targets multiple disease pathways, aiming for additive or synergistic effects with JAK inhibition.

• Data cut-off was February 20, 2026.

Efficacy results

• Selinexor plus ruxolitinib nearly doubled SVR35 rates at week 24 (50% vs 28%, p<0.0001), with rapid and sustained spleen reduction through week 36.

• Symptom improvement at week 24 was similar between arms, with no statistically significant difference in TSS.

• A promising overall survival signal was observed, with a hazard ratio of 0.43 (p=0.0222), indicating over 50% reduction in risk of death.

• VAF reductions ≥20% at week 24 were seen in 32% of combination patients vs 24% with ruxolitinib alone.

Safety and tolerability

• Safety profile was consistent with known effects of selinexor and ruxolitinib; no new safety signals identified.

• Most common adverse events in the combination arm: thrombocytopenia (59%), anemia (57%), nausea (57%), constipation (32%), neutropenia (27%).

• Grade 3+ adverse events occurred in 70% of the combination arm vs 50% in the control arm.

• Discontinuation due to adverse events was 14.5–15% in the combination arm and 8.6–9% in the control arm.

• Leukemic transformation rate was 1.7% in both arms.