The SENTRY trial is a study in myelofibrosis asking can we better the results for patients from a first-line therapy. Currently most patients with myelofibrosis receive a JAK inhibitor, usually that’s ruxolitinib which is our first available JAK inhibitor. But what we know about ruxolitinib is that the benefits for patients only generally last 2-3 years and underneath that, whilst we see prolonged survival, improved quality of life and spleen reduction, we don’t see a great deal of what we would call disease modification.

So in the SENTRY trial we added selinexor which is an XPO1 inhibitor which has at least four different ways in which it could add to the benefit of ruxolitinib. So it also inhibits JAK-STAT, it affects cell cycle, it affects apoptosis as well as NF-κB signalling.

So in this study we took JAK inhibitor naïve patients with myelofibrosis intermediate-1 risk or above, and treated them with a combination of selinexor and ruxolitinib or placebo and ruxolitinib.

What were the key results?

The results of the study are that we see a significant increase in the number of patients that hit the primary endpoint which is a 35% reduction in spleen volume. This occurred fast and was also prolonged beyond… the timepoint was at 24 weeks but we saw it at also 12 weeks and it was still present at 36 weeks.

A second endpoint was symptomatic improvement. Whilst we didn’t see symptomatic improvement, we saw that symptoms were the same. So it’s important to note that in a sense the study missed that aspect of its primary endpoint. As we go on and look at other benefits for patients we very importantly saw an overall survival benefit, at least in the first 24 weeks, so within a median follow-up of 11 months we saw a substantial reduction in the risk of death. It’s very important to see if that pans out with longer follow-up but this could be a very important finding for patients.

This reduction in the risk of death correlated with spleen reduction which is something we know about in the field. But we also saw other aspects that were improved with the selinexor combination which were reduction in fibrosis, which is a key feature of the disease, and also a reduction in the frequency or variant allele frequency, VAF, of the driver mutation for patients was greater for patients treated with selinexor. Which, all taken together, suggests that patients were living longer because probably the combination was modifying the disease.

Of course it’s also important to speak of safety. We know a lot about the safety of selinexor, it’s been given to tens of thousands of patients with other haematological conditions, principally but not only myeloma. The adverse effects we saw for patients were really those we would expect to see – some nausea, generally controlled, some fatigue, also generally controlled, cytopenias etc. There were more side effects in the combination arm but overall discontinuations in this study, which continues to be blinded, were equal between the two arms, speaking to some extent to tolerability.

What could be the clinical significance of these results?

The initial significance of these findings are that there may be a combination that can give us a tractionable benefit above and beyond JAK inhibitor therapy alone. But, of course, this is a disease that patients have for longer than six months so we do need to see further follow-up. But I personally find these results very exciting and to offer a lot of hope for our patients.

There are other things that are coming and that are being reported at the EHA meeting that are very relevant to listeners that might be interested in myelofibrosis. These include, for example, the data from the randomised phase III INDEPENDENCE study with luspatercept, looking to see benefit in anaemia with patients on ruxolitinib. Also the study from Insight of the calreticulin-targeted therapy which is really a very novel therapy in MPN in patients with myelofibrosis. There are three presentations at this meeting, really building on the very, very exciting data with these new targeted therapies.

Then, finally, we have a type 2 JAK inhibitor from a company called Ajax which has just been acquired by Lilly where data is being presented in patients with  myelofibrosis for the very first time. So these are all very exciting things that are being presented at EHA 2026.