ASH 2023 | XPORT-MF-034: selinexor + ruxolitinib combination therapy for MF

There is excitement about combining drugs in myelofibrosis, moving to combination therapy. The next trial is a combination of selinexor, the XPO1 inhibitor, plus ruxolitinib versus ruxolitinib plus placebo in JAK inhibitor-naive patients with intermediate and high-risk disease. And this is based on Phase II data demonstrating very significant clinical activity of selinexor plus ruxolitinib in JAK inhibitor-naive patients, both in terms of spleen, symptom, blood count stability, with no significant increase in toxicity. So the only way we can prove that the combination is better is a Phase III study, and that’s what’s now launched and enrolling globally. 

So I think what makes selinexor interesting in this area is it affects multiple pathways that are relevant to the pathobiology of the disease. So there’s a lot of preclinical rationale. There’s a lot of ongoing correlative studies to demonstrate pharmacodynamic effects that are meaningful with this drug. And what we’ve seen with some of the early data is that even at low doses of ruxolitinib, you can see clinical activity with selinexor. And I should point out that selinexor in combination with ruxolitinib in these studies is dosed lower than the approved dose in myeloma. So we’re talking about 60mg once a week.