My name is Doctor Paul Richardson, and I serve as the clinical program leader and the director of clinical research at the Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute in Boston, Massachusetts.
So one particular aspect of our work I wanted to have the privilege of sharing with you and your audience has been led by my colleague, Doctor Clifton Mo, which has been the innovative exploration of the combination of mezigdomide and selinexor with low-dose dexamethasone in relapsed refractory myeloma and classically in patients who have been previously exposed to BCMA-based therapies.
And this combines the potent cereblon E3 ligase modulator mezigdomide, oral one milligram a day, three weeks on, one week off, combined with low-dose dexamethasone, with the weekly dosing of selinexor, which is an exportin-1 inhibitor, so-called XPO1 inhibitor that is FDA-approved and highly active, particularly in high-risk disease, extramedullary disease, and in patients who have 17p deletion.
Another very interesting property of both oral agents is they're able to restore immune activity and enhance or reverse immune exhaustion. This is very important.
So in our study, we were able to not only show this, that in fact we in the patients that we've been able to analyze so far, T-cell subsets were augmented and improved with mezigdomide and selinexor combined. But most importantly, and this I think is critical, they were exquisitely active in patients who were BCMA-resistant or refractory.
So our response rates are very encouraging. The safety profile so far seems very manageable. And above all, we sort of saw Cliff, as rather shown this wonderful T-cell effect that it seems to bode well for how we might sequence therapies, in particular around immune treatments using mezigdomide and selinexor intelligently to boost the immune system at the appropriate time, but also raises the opportunity to take this combination earlier and use it when maybe one might want to keep a more aggressive cellular therapy or bispecific T-cell engager in reserve.
Speaking to patients of my own who participated in the trial, one is very classic: a lovely gentleman candidate for CAR-T therapy who really wanted to perhaps wait and see, keep the CAR-T in reserve. There was also some question of some degree of immune exhaustion because of relatively recent chemotherapy. And so we entered him into this trial. He's done exquisitely well. And in fact, his response is of such high quality that now he's in complete remission. He actually has chosen to defer his CAR-T further and continue on the oral therapy, which has been well tolerated in his case.
A second example is really quite remarkable. One of my patients who had unfortunately had cilta-cel, had a great response, but it only lasted ten months. Since then his disease came back very aggressively. He is 17p deleted. And so we were able to give him the mezigdomide and selinexor, but he had some issues with a very nasty viral infection in his lungs. As a result, he had some real issues with pulmonary function. In any event, with appropriate dose reductions and appropriate supportive care, including the judicious use of steroids, we've been able to actually treat him at very low doses of the mezigdomide and selinexor.
And remarkably, we've seen dramatic light chain response. Most interestingly, we've seen extramedullary disease that had literally been the size of a baseball on the left side of his chest disappear completely. So we've been very pleased with these results. Now, obviously, these are anecdotal reports, and I covered to some extent in this presentation, but they exemplify what we see as the value of this potential combination and adding it to our therapeutic armamentarium for our patients in this relapsed refractory setting.
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HealthTree • December 19, 2025