Transcript: Unmet needs in MM
Enrique Ocio, MD, PhD
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Right, so as you say, we have seen several evolutions in multiple myeloma in the last years and we have had like the PIC meets CD13 monoclonal antibodies, then all the immunotherapy that came along. But also we have some of the other gaps with novel mechanism of action that are really important. These have completely changed, 19 agents approved, these have completely changed the landscape of multiple myeloma patients.
Both, first line, also first relapses and subsequent relapses. And we have very good options for them. But as you say, there are several, still several unmet medical needs important to address. One of them is second line. Those patients are refractory that are refractory to daratumumab and lenalidomide. These patients in second line could have good options such as CAR-Ts for instance or other combinations. But particularly these, there are some of these patients that are not candidates for them because they have not received, for instance, proteasome inhibitors or because some of them may be dara-refractory or anti-CD13 monoclonal antibodies, risk refractory and they cannot receive combination with that. So I think these patients dara-, len-refractory. are an unmet medical need.
Also, there is another one which is those patients after immunotherapy. So when we are using this bispecifics, these CAR T-cells, BCMA, GPRC5D, this is fine, but they relapse. Then after this relapse, we have novel or new mechanisms of action to treat and to address this necessity. So in this second line, which is important, as I said, there are several options there, but particularly those patients that are, those patients that are daratumumab and lenalidomide refractory, those patients that are, many of them are coming from DRd now 'cause it's the standard of care for our elderly for non-transplant candidate newly diagnosed myeloma patients, when they relapse, they are dara and len refractory usually. What can we give them? They are not candidate for CAR-Ts, they are dara-refractory. So we cannot use anti-CD38 monoclonal antibodies in the second line. So we need something new. Here, we have several options.
We have PVd for instance, it could be an option. We have also Kd, also in this, is an old regime. We usually like to combine this. And also I think we have what we are now speaking is the selinexor, for instance, selinexor, bortezomib, dexamethasone. What I think is very attractive option for these patients, selinexor is a novel mechanism of action. These patients have not been exposed to them. It's combined with bortezomib, PI. These patients are also PI naive. So I think this could be something very interesting for this particular population, patient population. We could have other ones, but I think these ones are the ones that we currently have in our country, particularly in Spain and this is particularly interesting. So as I said and you also mentioned the, those patients after immunotherapy, after a CAR-T bispecific, so differences that have used T-cells to fight against the tumor. These patients after the relapse may have few options for them.
And we have, we, it's interesting to have the options for alternative that could restore the immune function. Selinexor you say the XPO1 targeting may have this function in the lymphocytes to restore the activity of these cells. And I think this could be very interesting for several points. One is to give them an anti-myeloma effect. And we are using this alone with con dexamethasone for instance. And we can see the activity of this, of this particular combination in this setting as a single agent, I would say with dexamethasone. But also we can use it as a bridging for instance.
'Cause sometimes we like to give an anti-BCMA followed by GPRC5D or the other way around. And in this case, I think having something that could restore, that could enhance the immune function to restore the functionality of this disease could be very attractive. So I see this selinexor as a good bridging strategy as a good partner for combinations that could also enhance this activity and something that we could use in the middle of or after this immunotherapeutic agent.
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MED-GL-2500132, March 2026