Karyopharm Phase 3 SENTRY Trial in Myelofibrosis Met First Co-Primary Endpoint
Key claim: In the Phase 3 SENTRY trial, selinexor plus ruxolitinib achieved statistically significant spleen volume reduction in myelofibrosis patients compared to ruxolitinib alone, with 32% vs 24% achieving ≥20% VAF reduction, though the symptom burden co-primary endpoint was not met.
Abstract
Karyopharm’s selinexor combined with ruxolitinib demonstrated statistically significant spleen volume reduction (first co-primary endpoint met) in myelofibrosis. Secondary data on symptom improvement (Abs-TSS) was not met. Variant allele frequency reduction showed 32% of combination-arm patients achieved ≥20% VAF reduction for JAK2, MPL, and CALR vs 24% on ruxolitinib alone.
Why this matters
SENTRY is another late-stage MF combination trial where spleen volume reduction was achieved but the symptom burden co-primary endpoint missed — reinforcing a pattern (similar to prior add-on trials) that mechanical/cytokine-driven spleen shrinkage does not reliably translate into patient-perceived symptom relief. For symptom management, this underscores that disease-modifying combinations cannot be assumed to address fatigue and constitutional symptoms, and that dedicated symptom-directed interventions remain necessary even when spleen response is robust.