Iberdomide Combos Post-ASCT in Myeloma: Eliminating Residual Disease (COMMANDER)

I'm Luciano Costa. I'm a myeloma physician in the University of Alabama at Birmingham. I'm here at the ASH meeting in San Diego 2024. And at this meeting, the consortium that we're part of, the COMIT consortium, is bringing some data on what we call the commander trial. My colleague Dr. Natalie Callender is presenting that as a poster. So the commander trial, the premise of that is, as we know, MRD positivity is an indicator of worse prognosis in multiple myeloma. And nowadays, most patients will achieve MRD negativity after induction therapy and transplant. But what about those who do not? And this trial was meant specifically to try to reverse or to induce MRD negativity and maintain MRD negativity in patients who are MRD positive after transplant using Iberdomyde, which is a cell mod. So for those who are not familiar, cell mods or cerebromodulators are oral drugs very much like Revlimid or pomelis, but they're kind of two generations up in the sense of being more, doing better what Revlimid and pomelis does, perhaps with less toxicity. So this trial initially combined Iberdomyde with daratumumab and dexamethasone for six cycles on patients who are MRD positive after transplant. And after six cycles, they go to Iberdomyde single agent maintenance. And then because this was done and was done safely, we tested all different doses without any problems. Then we opened the second cohort, which is Iberdomyde carfusomib, so now deploying the most active proteasome inhibitor we have in combination with Iber and daratumumab and dexamethasone to try to make those patients MRD negative. She's presenting the results of the part A, which is the dose finding. And the good news is all doses that we tested out of weight 1.6 milligram of Iberdomyde were well tolerated because Iberdomyde is being developed further at the one milligram dose. So that's the dose we're sticking to for the part two. The good news is the drug was well tolerated. Near half the patients on Iberdarodex converted to MRD negatively. Remember, many of those patients have received prior DARA before. So despite that, we're able to convert patients negative. And so far, every single patient on the quadruple therapy, most of which have received quadruple induction in our MRD positive after transplant, were able to convert to MRD negativity with Ibercarfusomibdarodex. So I think it's the first time we're seeing safety data for this very important combination. And I think that can be extrapolated to other settings of myeloma. That is a safe quadrupled regimen. But most important, it gives upper options in the future for patients who receive the best upfront therapy with quadruple, receive a transplant, and still have a stubborn disease that need to be dealt with, use a regimen that is well tolerated, and perhaps can lead to a deeper and longer lasting response.