EHA 2026 | The Phase III SENTRY trial: selinexor plus ruxolitinib in JAK inhibitor-naïve myelofibrosis

So we know what we can achieve with JAK inhibitors for myelofibrosis patients, but we also know the limitations of those therapies. So in brief, whilst we do see reduction in spleen and symptoms, there’s still improvements in that, many patients develop side effects and the benefits for patients are not enjoyed for generally longer than about three years or so. And therefore, in the field, we’ve been moving towards looking at combining a therapy with a JAK inhibitor with the aim of deepening the response, heading towards disease modification, but also keeping the response for longer and getting better benefits for patients. The difficulty with that, of course, is you can sometimes see combined toxicity because you’re using two agents rather than one. 

So in the SENTRY study, we used Selinexor, which listeners may be familiar with, of course, as an agent in myeloma, but that means as well that we have lots of experience in using that drug. In the SENTRY study, we took patients who were JAK inhibitor naive and randomized them two to one to receive selinexor plus ruxolitinib, just to emphasize the dose of selinexor for myelofibrosis is lower than we would use for myeloma. And tolerability appears to be better when it’s combined with ruxolitinib. These patients were compared to patients receiving placebo and ruxolitinib. So it’s placebo-controlled double-blind study. 

We’ve recently had a very exciting readout with almost double the number of patients having spleen responses. No benefit in terms of symptoms, but no worsening either, which is important. But just to note, of course, that does mean that they missed part of their key primary endpoint. But then along after that comes the exciting news that we see at least an early message of an overall survival benefit for patients with approximately a 50% reduction in risk of death, which is really exciting and very striking to see that in just six months. We didn’t even see that with JAK inhibitor versus placebo in six months. Of course, we will need to see longer follow-up to justify that signal. But also, interestingly, it correlates well with spleen volume reduction and spleen volume reduction is known to correlate with OS. And spleen volume reduction correlates with molecular response in this study. So there’s a signal that we could be heading to overall survival benefits through disease modification with selinexor, but we will need to see longer follow-up from that study.

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