Early SENTRY Data Suggest Benefit of Selinexor-Ruxolitinib in JAK Inhibitor–Naive Myelofibrosis: Claire Harrison, MD

Claire Harrison, MD, spoke with The American Journal of Managed Care^® (AJMC) ahead of the European Hematology Association (EHA) 2026 Congress about her abstract, “Selinexor Plus Ruxolitinib in Janus Kinase Inhibitor-Naive Myelofibrosis: Phase 3 SENTRY Trial,” which she presented during the late-breaking oral session.

Harrison, the study’s lead investigator, explained that the SENTRY trial (NCT04562389) compared selinexor plus ruxolitinib with ruxolitinib alone in Janus kinase (JAK) inhibitor-naive patients with myelofibrosis. As she reported at the EHA Congress earlier this month, the combination produced greater spleen volume reductions and was associated with encouraging early survival outcomes and reductions in mutant allele burden after a median follow-up of 11.6 months.

Symptom improvement was similar between arms. Meanwhile, the combination's safety profile was broadly consistent with selinexor's known effects in multiple myeloma. However, adverse effects appeared less pronounced, which Harrison attributed to ruxolitinib's anti-inflammatory and weight-promoting effects, as well as the lower selinexor dose used in the trial.

In this clip, she expanded on the findings, which suggest that adding selinexor to standard therapy may improve disease outcomes while maintaining symptom benefit.

According to Harrison, one of the most notable results was the higher rate of at least 35% spleen volume reduction among patients receiving the combination regimen. She noted that this clinically meaningful end point has historically been associated with improved long-term outcomes in myelofibrosis. Differences between treatment groups emerged as early as 12 weeks, indicating a rapid treatment effect.

Harrison also highlighted encouraging early survival data. At a median follow-up of 11.6 months, fewer deaths had occurred proportionally in the selinexor arm, resulting in an estimated HR of 0.43. Although follow-up remains relatively short and CIs are still wide, she described the signal as striking and worthy of further investigation. Additionally, causes of death were consistent with those typically seen in myelofibrosis, and rates of leukemic transformation appeared similar between treatment groups.

Beyond clinical responses, the trial provided evidence that selinexor may have disease-modifying potential. Harrison noted that approximately one-third of patients receiving selinexor achieved a 20% reduction in driver mutation variant allele frequency, and these molecular responses correlated with spleen volume reductions. Favorable trends were also observed in circulating blast counts and in preventing the emergence of new blasts over time.

Lastly, she emphasized that longer-term follow-up, including the planned 48-week analysis, will be critical to determining whether these early benefits translate into durable clinical advantages and potentially reshape frontline treatment for myelofibrosis.

"…if these results continue to play out in this way, this has the potential to change the way that we treat patients with myelofibrosis in an upfront setting…," Harrison said.