ASH 2024 | The value of selinexor in myeloma: current and future combinations and which patients may benefit

Selinexor has been around for some time. It’s not reimbursed in all countries. It’s a small company driving it. So they have two indications. One is monotherapy or with dexamethasone in penta-refractory patients. Very late line and they actually need to be penta-refractory. Not many other drugs have that strict sort of label. 

But they also have another approval, selinexor-bortezomib-dexamethasone in second line. And for the second one of these, the second line treatment, I think today is the time that this should have been approved everywhere, and it’s not approved in every country in Europe. But because now it’s fulfilling a space where we don’t have much. And the space I’m talking about is when you come from dara/len/dex, which has been the standard in the elderly, which is two thirds of the patients for a long time. When they progress, they are refractory to daratumumab, refractory to lenalidomide, and you don’t actually have any other triplet options that are very good, I would say. Selinexor and bortezomib, which is a novel mechanism for these patients after DaraRd and never seen a proteasome inhibitor before, and selinexor is also a completely new mechanism. It’s the only drug that has this nuclear transporter protein inhibitor mechanism. So that’s the perfect regimen today. 

That will be a challenge of course next year when belantamab-bortezomib-dexamethasone will be approved, it looks better, but as of now, this will be my drug of choice in second line after Dara-Len-Dex, or in those few patients who have been on Dara-Len maintenance after transplant but that’s still very few because this was just reimbursed this autumn. 

If it was reimbursed you could also use it in sort of other settings. We have very good data, from Phase II trials I have to say but still, with pomalidomide and with carfilzomib. And pomalidomide and carfilzomib, they also don’t have many combination partners after CD38 antibodies have been used. So if you have it available, that’s a possibility, let’s say after DaraKd or in second line, Selinexor-Pom-Dexamethasone for instance. There’s not so many options there. And carfilzomib after daratumumab doesn’t have anything to combine with from a Phase III trial and the data from the Phase II studies with Selinexor Kd and Selinexor-Pom-Dex are good. But it of course takes, and the countries are different here when it comes to flexibility around the label. Some countries need to stay strict on label and then it’s only Selinexor-Dex late or Selinexor-Bortezomib-Dex. Other countries can be a bit more flexible to combine with several drugs that are all reimbursed in some way.

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