The hazard ratio that will dominate conversations at EHA 2026 is 0.43: a more than 50 percent reduction in the risk of death observed in the combination arm of the phase 3 SENTRY trial, comparing selinexor plus ruxolitinib against ruxolitinib monotherapy in 353 JAK inhibitor-naive myelofibrosis patients. That number is preliminary, the overall survival analysis was not mature at the data cut, and the trial was not powered for OS as a primary endpoint. But it is the figure clinicians will probe hardest, because spleen volume reduction alone has never been enough to move the field.
On the primary endpoint that did read out, the combination delivered a clear signal. SVR35 at week 24 reached 49.8 percent in the selinexor-ruxolitinib arm versus 28.0 percent with ruxolitinib plus placebo, a statistically significant difference that held across all predefined subgroups, including patients receiving less than 15 mg of ruxolitinib daily. Spleen response was also rapid, with 49.4 percent of combination patients hitting SVR35 as early as week 12. A post-hoc analysis from the trial now presented at EHA suggests SVR35 itself may predict overall survival, a claim that, if validated, would meaningfully strengthen the regulatory argument for spleen response as a durable surrogate rather than a cosmetic one.
The second co-primary endpoint, absolute total symptom score improvement, did not separate from control. The combination arm improved by 9.9 points on the Abs-TSS versus 10.9 points with ruxolitinib alone, a non-significant difference. That miss matters for labeling discussions, but it is not fatal to the program. Myelofibrosis carries a median post-diagnosis survival of roughly six years in a population where fibrosis, splenomegaly, and cytopenia compound over time, and the variant allele frequency data, showing 32 percent of combination patients achieving reductions versus 23.9 percent in the control arm, opens a credible disease-modification narrative that the symptom endpoint alone could never sustain.
The single number to monitor from here is the overall survival hazard ratio at the final, protocol-specified analysis. A 0.43 HR from immature data is striking enough to anchor a regulatory conversation with the FDA, but it needs to survive maturity. If that OS signal holds when the trial crosses its predefined event threshold, the discussion around first-line myelofibrosis combination therapy changes materially.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
