IMS 2025: Linvoseltamab Shows Promise in High-Risk Smoldering Multiple Myeloma

In an interview with Pharmacy Times®, Paula Rodriguez-Otero, MD, PhD, associate professor and consultant in hematology at the University of Navarra in Pamplona, Spain, discussed the importance of studying high-risk smoldering multiple myeloma, as treating the disease earlier may allow for deeper responses and prevent progression to active myeloma. She highlighted her presentation, “Safety and efficacy of linvoseltamab in patients with HR-SMM,” which she shared at the 22nd annual International Myeloma Society (IMS) meeting and exposition in Toronto, Canada.

Rodriguez-Otero explained that linvoseltamab, a bispecific antibody targeting BCMA, has already shown strong efficacy in relapsed/refractory patients and is now being evaluated in this earlier setting. She noted that preliminary trial results show a 100% response rate, with many patients achieving very good partial or complete responses, suggesting promising potential for altering disease progression.

Pharmacy Times: Can you start by introducing yourself?

Paula Rodriguez-Otero, MD, PhD: My name is Paula Rodriguez Otero. I am a hematologist, and I work at the University of Navarra in Pamplona, Spain.

Pharmacy Times: What makes high-risk smoldering multiple myeloma such an important population to study, and why was linvoseltamab selected for evaluation in this setting?

Rodriguez-Otero: High-risk smoldering myeloma is an important patient population. Maybe I would just start briefly with monoclonal gammopathies. Multiple myeloma is the end stage of a disease that may begin in a precursor state called monoclonal gammopathy of unknown significance. Some of these patients may evolve into smoldering multiple myeloma, which is the stage before progressing to active disease.

We know that among these patients with smoldering multiple myeloma, we can identify those at high risk of progressing to active disease within the next two years. This is what we define as high-risk smoldering multiple myeloma. The idea is that if we target the disease at this earlier stage—before it becomes more heterogeneous and before it causes symptoms or end-organ damage—we may be able to cure the disease when it is much more sensitive. Intervening earlier may allow us to completely eradicate the disease and prevent complications.

Regarding the second question, why linvoseltamab? Linvoseltamab is a bispecific antibody targeting BCMA. It is already approved in both Europe and the United States for the management of triple-class exposed, relapsed/refractory multiple myeloma, based on data from the LINKER-MM1 study. This study involved heavily pretreated patients, all exposed to the three main classes of drugs. Linvoseltamab showed a high overall response rate, with deep and durable responses, and median progression-free survival was not yet reached with nearly two years of follow-up.

If we transfer this data into an earlier disease setting, where the immune system is more fit, we may be able to induce deep responses in most smoldering patients and ultimately prevent the disease from evolving into active myeloma.

Pharmacy Times: From the trial results, what efficacy signals suggest linvoseltamab could alter disease progression in HR-SMM?

Rodriguez-Otero: First, I must say the results are still preliminary. This is a phase 2 study that aims to enroll 40 patients. We are presenting data on the first 24 patients, with a median follow-up of only around four months.

What we see is that all patients achieved a response, giving us an overall response rate of 100%. Nearly 80% of patients had already achieved at least a very good partial response. The responses also deepened over time. For example, among the first six patients enrolled in the safety run-in phase, with a median follow-up of one year, 83% achieved a complete response.

We believe these data are very encouraging in terms of efficacy, with the majority of patients showing strong disease control.