Advances for Patients With High-Risk Smoldering Multiple Myeloma

At the 2026 LL&M Winter Symposium in Amelia Island, Florida, Victor Jimenez Zepeda, MD, Weill Cornell Medicine, New York, New York, discusses the evolving management of patients with high-risk smoldering multiple myeloma. 

Dr Zepeda highlights current FDA-approved options and emerging genomic and immunotherapy-based strategies, and highlights efforts to identify patients who may benefit from early intervention to delay progression and improve outcomes. 

Transcript:

My name is Victor Jimenez Zepeda, I'm a hematologist from Weill Cornell working at the myeloma center and the New York Presbyterian Hospital. 

I have been invited to participate in the LL&M Congress and it is with great enthusiasm that I've come here to talk about high-risk smoldering myeloma and what are the nuances for treatment, and what are the patients that could potentially be treated, when and how.

This is a particularly important topic and in the presentation that we have this weekend we discuss about how high risk smoldering myeloma has been defined over the years and how different clinical trials have been implemented and what is information that we learned from those clinical trials in terms of clinical outcomes, benefits in terms of decreasing the time to progression, but also the ultimate benefit, which is progression not only to active myeloma, but also decreasing the organ damage and also improving overall survival.

These days, we have a couple of treatments that are FDA approved for smoldering myeloma of high risk. One is the use of lenalidomide, and the other one is daratumumab. This is a little bit controversial and in the presentation over the weekend, we have actually reviewed all the pros and cons of getting treatment in this particular group. We have learned also that by using the novel strategies such as genomic-based features in patients with the smoldering myeloma, we could potentially define patients that may be more aggressive, and those are perhaps the patients that we could potentially use these novel strategies.

We're going to learn about this presentation also on the impact of novel therapies that have been investigated in clinical trials, and that's the use of immunotherapy, the use of CAR Ts, and even bispecifics in the setting of high-risk smoldering myeloma. In the weekend, we will be discussing about what are the patients that could potentially be discussed, what are the things to consider where we're presenting options for treatment in the high-risk smoldering myeloma group of patients, and what are the things that will come with the novel clinical trials.

This is a very exciting phase where we have novel treatments for active myeloma. Learning more about the high risk group could potentially help us understand if early intervention will potentially get patients with myeloma, at least from the perspective of getting treatments that are more meaningful, potentially the benefit of keeping them alive and hopefully making patients to live long enough that they die of something completely different, which is what we call functional cure. Getting to treat patients earlier could potentially have that benefit.

We're not there yet to say that the treatments that we have available today might be the ones that can change the features of high risk smoldering myeloma, but the fact that we have novel treatments that have been now investigated in this phase will help us understand what is the future and hopefully by intervening sooner, we will prevent all the damages that can come from getting the myeloma more active.

Source:

Zepeda V. Who will we treat in 2026? High-risk smoldering limited vs full-quad treatment. Presented at LL&M Winter Symposium; January 30-February 1, 2026. Amelia Island, FL.