EHA 2025 | A subgroup analysis of the BOSTON trial: selinexor dose reductions in LEN-refractory patients

In BOSTON trial, the combination of selinexor plus bortezomib and dexamethasone versus bortezomib and dexamethasone was conducted. And the results were good enough to give FDA and EMA approval for this combination. First of all, selinexor is the first in class XPO1 inhibitor that has a unique mode of action and this is because it retains in the nucleus oncoproteins and this eventually leads to plasma cell cellular death. In a subgroup of this analysis, LEN-refractory patients, which is a very common thing at this point, when patients with multiple myeloma in first line have received almost all of them daratumumab, lenalidomide and most of them also bortezomib become refractory, then the opportunity is to change the class of drugs and selinexor is a possibility in this case. So in the analysis of a subgroup of lenalidomide-refractory patients, the selinexor, velcade and dexamethasone combination gave very good results in this very difficult to treat population with a progression-free survival of almost 10 months against the six months which was for bortezomib and dexamethasone alone. It was also shown that patients in selinexor, velcade, dex had less adverse events in regards to peripheral neuropathy against bortezomib and dexamethasone. And also it was found that selinexor main adverse events were not hematological and even if they were hematological most of our physicians are able to treat. The most difficult part is non-hematological adverse events and this includes mainly fatigue and also nausea and vomiting and sometimes diarrhea. So it was shown that in all patients, regardless if they were len-refractory, the results were much better when there were dose reductions of selinexor, not starting with the dose that was 100 milligrams, but less doses like for example 40, 60 or 80 milligrams. And then according to the patient tolerance, this could be evaluated and there was dose escalation or not. So this study that I’m presenting today is about LEN-refractory patients and dose escalation of selinexor and it seems that in this cohort of patients that were also older and also had more high-risk cytogenetics than others, the results were very good when there is a selinexor dose reduction. So it was found that selinexor was very well tolerated, there were less adverse events and this had the result that patients stayed longer in the trial and so they benefit from better progression-free survival, overall response rate, of course safety and consistency with the therapy. As far as progression-free survival is concerned, there was a 14-month progression-free survival for SelVd patients and for velcade-dex patients this went down to five months. So I believe that this combination when it is modified and when the selinexor dose is adjusting, the benefit for the patient is unique and so the drug, which is very effective in many patients and also patients with high-risk cytogenetics, can reveal its potency and can show remarkable results.

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