Clinical Summary:

• Design/Population: Phase 3 SENTRY trial evaluating selinexor plus ruxolitinib versus placebo plus ruxolitinib in 353 JAK inhibitor–naïve patients with myelofibrosis and intermediate-1 or higher-risk disease.
• Key Outcomes: The combination achieved significantly higher spleen volume response rates at week 24 (approximately 50% vs 28%), was associated with deeper molecular responses, and demonstrated an early overall survival signal favoring selinexor plus ruxolitinib.
• Clinical Relevance: These findings suggest that adding selinexor to ruxolitinib may enhance disease control and potentially modify disease biology, supporting further evaluation as a frontline treatment strategy in myelofibrosis.

John Mascarenhas, MD, Mount Sinai Medical Center, New York, New York, discusses results from the phase 3 SENTRY trial evaluating selinexor plus ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis.

Compared with ruxolitinib alone, the combination significantly improved spleen volume reduction and was associated with higher rates of molecular response, including reductions in JAK2, CALR, and MPL variant allele frequencies. An early overall survival (OS) signal was also observed, although longer follow-up is needed to confirm the durability of this benefit.

These findings, presented at the 2026 ASCO Annual Meeting in Chicago, Illinois, support selinexor plus ruxolitinib as a potential disease-modifying approach that may improve long-term outcomes for patients with myelofibrosis.

Transcript: 

Hi, I'm John Mascarenhas from the Icahn School of Medicine at Mount Sinai in New York City. Today I'll be reviewing the results of the phase 3 SENTRY trial in JAK inhibitor–naïve patients with myelofibrosis.

SENTRY was a global, randomized, double-blind phase 3 study evaluating selinexor plus ruxolitinib versus placebo plus ruxolitinib in 353 patients with myelofibrosis who had intermediate-1 or higher-risk disease. Patients were randomized in a 2:1 fashion to receive selinexor plus ruxolitinib or placebo plus ruxolitinib.

The study demonstrated a significant improvement in spleen responses with the combination. At week 24, approximately 50% of patients treated with selinexor plus ruxolitinib achieved a spleen volume reduction of at least 35%, compared with approximately 28% of patients treated with ruxolitinib plus placebo.

Beyond the spleen responses, we also observed evidence suggesting that the combination may have disease-modifying activity. Patients receiving selinexor plus ruxolitinib experienced higher rates of molecular response, including reductions in JAK2, CALR, and MPL variant allele frequencies compared with patients receiving ruxolitinib alone. These findings suggest a deeper biologic effect beyond symptom and spleen control.

Another important observation was the emergence of an early overall survival signal favoring selinexor plus ruxolitinib. While the follow-up remains relatively short and additional data will be needed to determine whether this benefit is durable, the finding is encouraging and supports continued evaluation of the combination.

Overall, the clinical and molecular findings consistently favored selinexor plus ruxolitinib. The combination achieved superior spleen volume responses, was associated with deeper molecular responses, and demonstrated an early overall survival signal compared with ruxolitinib alone.

These results suggest that adding selinexor to ruxolitinib may enhance disease control and potentially modify the underlying biology of myelofibrosis. Presented at the 2026 ASCO Annual Meeting in Chicago, these findings support selinexor plus ruxolitinib as a promising frontline treatment strategy that may improve long-term outcomes for patients with myelofibrosis.

Source: 

Mascarenhas J, Ali H, Al-Ali HK. et al. Selinexor plus ruxolitinib in JAK inhibitor–naïve myelofibrosis: Phase 3 SENTRY trial. Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. Abstract 4513.