Advancements in Treating Patients with Precursor Disorders of Multiple Myeloma

At the 2025 Lymphoma, Leukemia & Myeloma (LL&M) Winter Symposium in Miami, Florida, Victor Jimenez-Zepeda, MD, Arnie Charbonneau Cancer Research Institute, Calgary, Alberta, discusses exciting clinical trials and updates on potential treatments for precursor disorders of multiple myeloma (MM), including smoldering multiple myeloma and monoclonal gammopathy of undetermined significance.

Transcript:

Hi, this is Victor Jimenez-Zepeda. I'm a hematologist from the University of Calgary, affiliated to the Arthur Child Comprehensive Cancer Center. Terminal Cancer Center. I was invited today to the Lymphoma Leukemia & Myeloma Congress, the Winter Symposium, here in Miami.

I was actually talking about smoldering multiple myeloma and monoclonal gammopathy of undetermined significance. This is an area that is really growing because now we have better tools to assess monoclonal proteins. There are some monoclonal proteins that are actually related to clinically significant entities, including large amyloidosis. But also, there are some patients that have smoldering myeloma, which is the pre-phase before actually patients truly have symptomatic disease that actually requires therapy.

There are some thoughts about the possibility of using treatments that can perhaps intercept the disease and also to give us perhaps some control, better control, by intervening sooner or perhaps even to cure. There are some clinical trials that have looked at in patients with smoldering multiple myeloma of high risk.

We presented today a little bit of data about the most recent, publication of AQUILA, which is a clinical trial, a phase 3 study where patients with smoldering multiple myeloma were treated with daratumumab or were just monitored actively without any treatment. The data was really exciting because patients have a benefiting progression-free survival and also overall survival.

But the treatment that we have with daratumumab monotherapy is not necessarily the treatment that we do for patients with myeloma, which these days we actually do quadruplet therapy, including daratumumab itself, but also [dexamethasone] (RVd) or the KRd. So, the question remains whether we're actually selecting properly the patients that truly need treatment or whether we might have to focus more on the patients that are more aggressive, not only just by the regular definitions of high risk of smoldering, but also looking at patients that truly have a more aggressive phenotype and need to be treated more like myeloma.

This was matter of debate because as you know, in the US, lenalidomide and dexamethasone is approved for the treatment of high-risk smoldering myeloma. The question that we have is whether daratumumab monotherapy might be enough or if this might be too much for some people because we're talking about smoldering myeloma disease without symptoms. It's just the odds for these patients to actually progress into symptomatic myeloma required therapy.

This was really exciting to have a conversation and it was matter of debate about which patients to treat, if there is any, what may be the best treatment for that. And I think the answer might be the, perhaps with a better correlative studies, we could define the population that truly need to be considered more like MGUS and just move to another definition of patients with myeloma that do have symptoms or that might be a higher risk to progress in the first year and perhaps that population be treated more like symptomatic myeloma.

That will be the future. Like anything, the way we learn is by doing clinical trials. Now we have clinical trials looking at novel approaches that, include the use of CAR-T, that is a static CAR-PRISM that was also presented in the American Society of Hematology meeting in the last year using CAR-Ts. This is controversial as CAR-T does have some long-term side effects. But just to say that it's been investigated, and the clinical trial is the best way for us to learn whether this is strategy might be the best way to go.

There is also the use of bispecifics that are in the investigation, in the high-risk smoldering myeloma. And that's a case of talquetamab and teclistamab and more data is to be reported.

With that, I would like to thank the organizers for the invite, and it's been a pleasure to be here in Miami. Thank you.

Source:

Jimenez-Zepeda V. Updates in Precursor Disorders. Presented at Lymphoma, Leukemia & Winter Symposium; February 7-9, 2025. Miami, FL.