SENTRY Trial Shows Survival, Spleen Benefits in Myelofibrosis: Claire Harrison, MD

Ahead of the European Hematology Association 2026 Congress in Stockholm, Sweden, Claire Harrison, MD, discussed with The American Journal of Managed Care^® the rationale and key findings of her abstract “Selinexor Plus Ruxolitinib in Janus Kinase Inhibitor-Naive Myelofibrosis: Phase 3 SENTRY Trial,” which she presented this afternoon during the late-breaking oral session.

Harrison, the study’s lead investigator, explained that while ruxolitinib (Jakafi; Incyte), the first Janus kinase (JAK) inhibitor approved for myelofibrosis approximately 15 years ago, remains a cornerstone of treatment, it does not fundamentally alter the disease course, leaving a significant unmet need.

To address this gap, the SENTRY trial (NCT04562389) evaluated selinexor plus ruxolitinib based on selinexor’s mechanisms relevant to myelofibrosis pathogenesis, including inhibition of JAK/STAT and NF-κB signaling, induction of cell-cycle arrest, and enhanced apoptosis via the TP53 pathway through XPO1 inhibition.

Across disease subtypes, the combination produced rapid, deep, and sustained reductions in spleen volume vs ruxolitinib alone. She added that symptom improvement was comparable between arms, as patients in the control arm derived similar symptom benefits.

However, the combination demonstrated a survival advantage at a mean follow-up of only 11 months, a finding Harrison described as striking. That survival benefit correlated with spleen volume reduction, consistent with established field knowledge. The combination arm also showed greater reductions in mutant driver allele fraction, suggesting potential disease modification.

Harrison highlighted that selinexor has an established safety profile from extensive clinical use in myeloma. In SENTRY, the safety findings were broadly consistent with that experience, though adverse effects appeared less pronounced. Harrison attributed this to 2 mitigating factors: the anti-inflammatory, weight-promoting effects of the ruxolitinib backbone and the lower selinexor dose used in SENTRY compared with myeloma studies.

“It's important to remember that in this study, number 1, there was a combination with ruxolitinib, which is an anti-inflammatory drug, where patients often gain weight,” she concluded. “The dose of selinexor in this study is lower than the dose that is used in myeloma, so many of the side effects that colleagues working in the myeloma field may have seen with this drug were not quite so predominant.”