What’s Next in Multiple Myeloma: Smoldering, High-Risk, and Frontline Therapy

Dr Thomas Martin previews his SOHO 2025 session and explores the pressing next questions in multiple myeloma, including when to treat smoldering disease, how to better define and manage high-risk patients, and how innovations like bispecifics and CAR T-cell therapy may reshape frontline treatment and bring the field closer to a cure.

Please introduce yourself by stating your name, title, and any relevant clinical experience you’d like to share.

Thomas G. Martin III, MD: Hi, I am Dr Tom Martin from the University of California, San Francisco. I have been treating patients with multiple myeloma for 30 years and have been the lead for the educational program for myeloma at SOHO for close to the last decade.

Can you provide an overview of your session at SOHO 2025?

Dr Martin: I am going to talk at SOHO on Saturday about next questions for multiple myeloma. What I want people to understand is there are quite a few important next questions in multiple myeloma. I have 10 minutes. I am not sure I'm going to be able to get everything in in 10 minutes, but I'm going to try.

The first question is: what are our next steps for treatment of smoldering multiple myeloma? We're going to have 2 sessions on smoldering myeloma. We're going to have, on Wednesday, a case presentation and then a discussion by Dr Saad Usmani. I'm going to talk about the next steps and the next questions there.

The next questions are: how are we all going to uniformly adopt treatment for smoldering myeloma? Currently, people are very hesitant to initiate therapy in smoldering multiple myeloma. I'm going to talk what we need to do to break the ice so that we are all comfortable treating the appropriate patients with smoldering myeloma.

The next thing I'm going to talk about is the treatment of high-risk multiple myeloma. As our definitions have evolved for high-risk disease, the next questions are: what studies are we going to do to assess people at diagnosis and determine whether or not they have the new high-risk diagnosis of multiple myeloma?

I'm going to talk about studies that people can do so that they will be able to categorize patients the way we do right now in the new International Myeloma Working Group (IMWG) high-risk criteria. That will be really interesting.

Finally, I'm going to talk about the direction we are headed in for treatment of newly diagnosed multiple myeloma. We now treat patients with quad-based therapy and are expecting to have progression-free survival (PFS) on the order of approximately 7 years in transplant-eligible patients, and up to 10 to 15 years of PFS in some transplant-eligible patients from the first line of therapy, which is amazing.

But can we cure multiple myeloma from the frontline? What are we going to do there? I will talk a little bit about the incorporation of bispecifics in frontline therapy and the incorporation of CAR T-cell therapy in myeloma. What's next on the docket for bispecific and CAR T-cell therapy? For bispecifics, it's the use of combination-based therapy and earlier integration into treatment—including, like I just said, frontline therapy.

We also have many novel technological advances that we're looking forward to in CAR T-cell therapy. I call it the “3 Ts”, we have improvements in the targets, the technology, and the treatment population. Those 3 Ts are going to allow us to get to a scenario where, hopefully, we are curing more patients with multiple myeloma.

What I mean by that is, these patients will never have to have treatment again for myeloma and, hopefully, will also be off therapy for myeloma. They won't need maintenance therapy for 5 or 10 years or ongoing. That's what I'm going to try to talk about in 10 minutes.

Is there anything else you hope audiences will take away from this session?

Dr Martin: What I hope that audiences take away from this is that our newer therapeutics and diagnostics are here to stay. We're going to have to use all these new diagnostics. We'll talk about some of the new diagnostics, including MRD testing. Everybody is going to have to be able to use bispecific, T-cell engaging antibodies.

I know there's a learning curve, and I know it's difficult in a lot of practices to initiate therapy with a bispecific antibody, but it is going to be the treatment for the majority of patients with myeloma. I also think it will be the treatment for the majority of patients with cancer going forward because they have had such a profound, positive effect. So, people are going to have to learn how to do it.

In terms of CAR T-cell therapy, it's going to be difficult with current technologies, which require lymphocyte collection and a complex chain of command—sending cells to the manufacturing company, returning them to the treatment center, and then administering them to the patient. That's difficult. Many centers won't be able to do that.

However, with the development of in vivo CARs—where the vector is delivered directly via intravenous injection, eliminating the need for T-cell collection and lymphodepleting therapy—the landscape may change. If this technology proves to be as effective as anticipated, CAR T-cell therapy could potentially be administered in many more community centers than is currently possible.