Hi, my name is Ben Diamond. I'm an assistant professor at the University of Miami. And today, I'll be talking to you guys about a trial that we've developed, which is a quadruple hit regimen for drugs, built around a backbone of a drug called iberdomide, which is a drug that's been in development for a while. It's a CELMoD or a cereblon E3 ligase modulator. And it's sort of the natural evolution of the IMiDs that you might be more familiar with lenalidomide, pomalidomide. It's the same kind of mechanism of action, but a more potent drug, with a better side effect profile.
And so our thinking for this trial was basically that you know, in the early relapse setting for multiple myeloma, most patients have developed lenalidomide refractory unfortunately. And the triplet regimens that we tend to use in the early relapse setting are sort of suboptimal for these kinds of patients. And furthermore, you know, as you're well aware, those triplet regimens, they get used until progression, right? So that's a lot of infusions. And it gets a little burdensome and cumbersome.
And so we figured that by leveraging Alberta Mind, which is kind of effective in a lenalidomide resistant setting, we might be able to capture back those deep responses that we saw with induction therapy and then to eventually allow for the opportunity to de-escalate back down to monotherapy with iberdomide, which should be very good for quality of life. All right.
So the trial is called rekindle. It's re induction with carfilzomib, iberdomide, daratumumab for long term efficacy and eligible patients. We had 32 on the trial. Eligible patients had 1 to 3 prior lines of therapy. Daratumumab or isatuximab in the past was okay as well as carfilzomib in the past was okay. As long as there had been no relapse on those drugs and no intolerable toxicities, and then patients would enroll to get 8, 28 day cycles of this combination of four drugs iberdomide, daratumumab, carfilzomib, and dexamethasone, for eight months it cycles.
And at the end of that you would do a bone marrow biopsy looking for MRD negativity, either by flow cytometry or by adaptive clonoseq. And regardless of that response, although that was the primary endpoint, regardless of that response, you would then de-escalate and begin up to three years or 36 cycles of iberdomide monotherapy.
So our results look honestly quite good. So to date, our overall response rate is 100%. So all patients have responded. And then for our MRD negativity results, the primary points at ten to the negative fifth, the rate of 71%, for the 24 assessable patients at the time of the data cutoff. And to kind of put that into context for you, similar trials in this setting, with lenalidomide refractory populations, that rate tends to be more in the 10 to 15 to 20% range. So this is a significant improvement.
Now for safety, how tolerable isn't. Right. Because this is a new combination. We haven't used these four drugs together before. So hematologic toxicities were common. This is stuff like low white blood cell count. Stuff that you don't necessarily feel, but things that we are worried about because they put you at risk for infection. And so neutropenia was one of the biggest sort of expected toxicities. But no patients discontinued the treatment because of, you know, a larger toxicity. And we were able to growth factor to try and, you know, prevent some of those those detriments to white blood cell count.
For the rest of the safety for non hematologic toxicity. Well, we're really happy to see is that, you know, as you guys are well familiar with toxicity. It's a lenalidomide and pomalidomide can include rash and fatigue and diarrhea and clots. These are things that we all get concerned about with IMiDs. We really didn't see very much of that with this combination. Sort of speaking to the tolerability of iberdomide. We're very happy to see the low rates there. Other expected toxicities, but generally very well tolerated.
So, in summary, very well tolerated regimen, for this 1 to 3 prior line setting for lenalidomide refractory patients. Good efficacy, 71% MRD negativity at the 10th and negative fifth level. And sort of in this evolving landscape with T-cell redirection, it's tough to try and figure out exactly where this fits, but we sort of think that maybe either before or in between T-cell redirecting therapies, we have an extremely potent, well tolerated regimen that lets patients de-escalate down to a monotherapy once they've achieved a good response.
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HealthTree • December 18, 2025