SOHO 2025 Highlights: Redefining Risk and Treatment in Smoldering Multiple Myeloma

Dr Sagar Lonial discusses his SOHO 2025 case presentation on evolving definitions of high-risk smoldering multiple myeloma, the growing evidence for early intervention, and how innovations such as CAR T-cell therapies and bispecific antibodies are shaping the future of myeloma treatment.

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

Sagar Lonial, MD: I'm Sagar Lonial. I'm chair and professor of the Department of Hematology and Medical Oncology at Emory University School of Medicine and the chief medical officer for the Winship Cancer Institute.

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

Dr Lonial: At SOHO 2025, I talked about a case of a patient who had high-risk smoldering myeloma by virtue of more than 20% plasma cells in the bone marrow, as well as an M protein greater than 2.

The point of that was to illustrate the fact that I think we, as a community, have identified what the definitions of high risk are. It's not perfect but certainly gives us some food for thought. It was also to demonstrate the use of either lenalidomide, lenalidomide plus dexamethasone, or the CD38 antibody daratumumab as early intervention or prevention in these kinds of patients. We reviewed data from a number of trials that demonstrated that early intervention could, in fact, impact time to develop myeloma and, in the case of the AQUILA trial, even improve overall survival.

What were your biggest takeaways from the conference regarding multiple myeloma?

Dr Lonial: I think what was really exciting to see in myeloma is not only the depth and breadth of new, potential treatment options, but moving a lot of these treatment options—such as CAR T-cell therapies or bispecifics—into earlier lines of therapy, and potentially even moving them into frontline therapy.

What I also really enjoyed hearing from a number of my colleagues was the idea that there are likely subsets of patients who can potentially be cured, and that taking an aggressive to approach early on is more likely to get us down that road.

How do you balance early treatment of high-risk smoldering multiple myeloma with concerns about overtreatment and toxicity?

Dr Lonial: As we think about early intervention for the smoldering multiple myeloma patient population, it's important to recognize that the idea of toxicity was a major concern when all we had were alkylating agents and corticosteroids. That has now not been borne out with the use of IMiDs and the use of the anti-CD38s.

There are early trials looking at CAR T-cell therapies and bispecifics where I think the toxicity and safety question still is yet to be answered. But, certainly, with the less intensive therapies, we’re clearly not adding a lot of toxicity to a patient's experience.

From the overtreatment perspective, if you prevent a patient from needing therapy, I don't know if that's overtreatment. To date, there has been no demonstrable evidence that treating them early impacts their subsequent progression-free survival or overall survival. While it is a theoretical concern, I don't think overtreatment has been borne out in the literature.

Is there anything else you hope audiences took away from your session?

Dr Lonial: I think that there are a lot of really exciting, innovative approaches to managing patients with smoldering multiple myeloma.

The definition of smoldering multiple myeloma, and particularly high-risk smoldering multiple myeloma, does continue to evolve. Making sure you're partnering with a major myeloma center so that your patients get access to the latest and greatest in terms of clinical trials, as well as potentially diagnostics, is really important—particularly in a field moving as fast as myeloma.