SENTRY phase III: Selinexor + ruxolitinib for JAKi-naïve MF

Results from the global, double-blind, randomized, placebo-controlled, phase III SENTRY trial (NCT04562389), evaluating selinexor + ruxolitinib (n = 235) vs placebo + ruxolitinib (n = 118) in patients with Janus kinase inhibitor (JAKi)-naïve myelofibrosis (MF), were presented by Claire Harrison at the European Hematology Association (EHA) 2026 Congress, June 11–14, 2026, Stockholm, SE. The coprimary endpoints were spleen volume reduction ≥35% (SVR35) and change in absolute total symptom score (AbsTSS; excluding fatigue) at Week 24. 

Key data: At Week 24, SVR35 was achieved by 49.8% of patients in the selinexor + ruxolitinib arm vs 28.0% in the placebo + ruxolitinib arm (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.60–4.17; one-sided p < 0.0001). The change in AbsTSS from baseline to Week 24 was similar between groups (−9.9 vs −10.9; one-sided p = 0.825). Overall survival (OS) favored selinexor + ruxolitinib (hazard ratio [HR], 0.43; 95% CI, 0.19–1.00; nominal one-sided p = 0.022). Variant allele frequency (VAF) reduction ≥20% at Week 24 was higher with selinexor + ruxolitinib than placebo + ruxolitinib (32.0% vs 23.9%) and was associated with achieving SVR35 (nominal one-sided p < 0.001). Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 70.1% of patients in the selinexor + ruxolitinib vs 50.0% in the placebo + ruxolitinib arms. 

Key learning: Selinexor + ruxolitinib achieved rapid, deep and sustained SVR35, with an early OS signal but no additional TSS benefit, vs placebo + ruxolitinib in JAKi-naïve MF, representing a novel treatment strategy in this setting.