Prof Claire Harrison speaks to ecancer about results from the phase 3 SENTRY trial evaluating selinexor, an XPO1 nuclear export inhibitor, in combination with ruxolitinib in patients with Janus kinase inhibitor (JAKi) naïve myelofibrosis.

Myelofibrosis is a myeloproliferative neoplasm characterised by splenomegaly, severe symptoms, and reduced survival, with limited durable responses to current standard therapy with ruxolitinib alone.

Dr Harrison highlights that in this randomised study of 353 patients, the addition of selinexor to ruxolitinib significantly improved spleen volume reduction at week 24 compared with ruxolitinib alone, with nearly half of patients achieving a spleen volume reduction of at least 35 percent.

Responses were rapid, sustained, and associated with improvements in disease biology, including reductions in driver mutation variant allele frequency and circulating blasts. Symptom improvement was comparable between treatment arms.

At longer follow-up, overall survival favored the combination arm, and achievement of spleen response was associated with improved survival outcomes.

These findings support selinexor plus ruxolitinib as a promising disease-modifying combination therapy in JAK inhibitor naïve myelofibrosis.