Late-breaking phase 3 data show significantly improved spleen responses and an early survival signal with selinexor plus ruxolitinib, supporting a possible disease-modifying role in frontline myelofibrosis
touchHEMATOLOGY coverage of EHA 2026
The addition of selinexor to ruxolitinib significantly improved spleen responses and generated an early signal for overall survival benefit in patients with JAK inhibitor–naïve myelofibrosis (MF). This is according to late-breaking phase 3 SENTRY data presented by Prof Claire Harrison (Guys and St Thomas NHS Foundation Trust, London, UK) at the European Hematology Association (EHA) 2026 Congress . The findings position the XPO1 inhibitor as a potential new partner to ruxolitinib in the frontline setting, with emerging evidence of disease-modifying activity.
Abstract LB5002: Harrison C, Al-Ali HK, Gutierrez VC, et al. SELINEXOR PLUS RUXOLITINIB IN JANUS KINSE INHIBITOR–NAÏVE MYELOFIBROSIS: PHASE 3 SENTRY TRIAL. Presented at: EHA 2026, Stockholm, Sweden. June 11–14th, 2026.
“SENTRY is a landmark study in myelofibrosis. This is proof of principle that we need to move towards new treatment paradigms.” said Prof Claire Harrison, the study’s lead investigator.
What did the data show
The SENTRY trial (NCT04562389) randomized 353 patients with JAK inhibitor–naïve MF 2:1 to selinexor 60 mg once weekly plus ruxolitinib (n=235) or placebo plus ruxolitinib (n=118). Eligible patients had a spleen volume ≥450 cm³, active symptoms, Dynamic International Prognostic Scoring System (DIPSS) intermediate-1 risk or higher, and platelet counts ≥100×10⁹/L. The co-primary endpoints were spleen volume reduction ≥35% (SVR35) and absolute mean change in total symptom score (AbsTSS), excluding fatigue, at week 24.
The trial met its spleen endpoint, with SVR35 achieved in 49.8% of patients receiving selinexor plus ruxolitinib compared with 28.0% receiving ruxolitinib alone (OR 2.58; 95% CI 1.60, 4.17; p<0.0001). Responses were rapid and sustained, with rates of 49.4% versus 20.3% at week 12, 46.9% versus 23.0% at week 36, and 67.7% versus 44.9% at any timepoint. Mean spleen volume reduction at week 24 was −40.0% versus −26.7%.
The symptom endpoint was not met, with mean AbsTSS change of −9.9 (−11.2, −8.6) versus −10.9 (−12.6, −9.1), respectively (adjusted mean difference 0.97; 95% CI −1.07, 3.02; p=0.825). However, exploratory analyses showed driver mutation variant allele frequency reduction ≥20% in 32.0% versus 23.9%, while selinexor plus ruxolitinib reduced circulating peripheral blasts in patients with detectable baseline blasts.
Key clinical takeaway
For Professor Claire Harrison, the data suggest that adding selinexor may extend beyond improving spleen responses. “SENTRY is a landmark study in myelofibrosis,” she said, noting that selinexor’s multiple complementary mechanisms make it a rational partner for ruxolitinib. “We saw a near doubling of spleen response, with no worse symptom outcomes.”
Although follow-up remains short, overall survival favored the combination (HR 0.43; 95% CI 0.19, 1.00; nominal p=0.022), with 95.3% versus 89.8% of patients alive at median follow-up of 11.6 and 12.6 months. A landmark analysis further linked SVR35 to survival, with 98% of responders versus 88% of non-responders alive at week 72.
Toxicity was higher with the combination, with grade ≥3 treatment-emergent adverse events in 70.1% versus 50.0%, largely driven by cytopenias. Harrison noted there were “no unexpected adverse events”, and highlighted ongoing work evaluating selinexor as monotherapy before JAK inhibitor introduction.
With longer follow-up now needed, SENTRY provides the strongest evidence to date that combination approaches in frontline MF may improve not only spleen control, but potentially survival.
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This content has been developed independently by Touch Medical Media for touchONCOLOGY and touchHEMATOLOGY. Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media. This article was created by the editorial team utilizing AI as an editorial tool (ChatGPT 5.5 [Large language model]. https://chat.openai.com/chat.) The content was developed and edited by human editors. No funding was received in the publication of this article.
Cite: Phase 3 SENTRY trial positions selinexor plus ruxolitinib as potential new frontline option in myelofibrosis. touchHEMATOLOGY. 1st July 2026.
