Highlights of Smoldering Multiple Myeloma from ASH25 | Mohamad Mohty, MD, PhD

Hi. I'm Mohamad Mohty from the Sorbonne University and Saint-Antoine Hospital in Paris, in France. And it is my great pleasure to be with you at this ASH 2025, annual meeting. In, the lovely city of Orlando.

So I've been asked to discuss, smoldering multiple myeloma and what's new there. Well, obviously, this is a very hot topic. Lots of controversies, lots of opinions, lots of debates. But there are some good news.

First of all, I would say now we're trying to detect multiple myeloma earlier. We're trying to intervene earlier. And this is exactly, I think, that philosophy we should follow for the future, trying to, avoid actually the disease and its deleterious symptoms.

Now, having said this, it's not so easy. Historically, smoldering multiple myeloma, who was in the category of the wait and watch. We had then some good studies with lenalidomide single agent. They proved efficacy, but unfortunately adoption didn't follow because the community didn't feel that this will modify the natural history of the disease.

More recently, we had the AQUILA trial showing that there are tumor, maybe a monoclonal antibody directed against CD38 single agent can provide a true benefit for smoldering multiple myeloma. Of course, we can spend hours debating about the design of the trial, the inclusion criteria, and whether this is relevant for the practice in 2025 or 2026.

And of course, for patient, the big question, should we give them daratumumab for every so smoldering multiple myeloma. The answer is not easy. The drug daratumumab is approved now for smoldering multiple myeloma. But I think we remain in the gray zone.

The great added value of the AQUILA trial is about establishing a sort of a benchmark, sort of a imperative with daratumumab. The next step is to figure out whether we have better combinations, better agent, because I think it's rather more important to get rid of the disease, the evolution to myeloma, rather than delaying the evolution to myeloma.

So you can see it's a sort of a philosophical, problem. So with this in mind, I think at this ASH 2025 meeting, we've seen some interesting data about the use of immunotherapies like bispecific antibodies, T-cell engagers, but also Car-T cells with the goal really to eradicate the myeloma clone.

And this is extremely promising. Obviously, we're still in the beginning of the story. But I think the future looks bright. And I'm quite optimistic that at some point we will be able to act very early, very quickly, and, of course, avoid the development, of multiple myeloma.