Linvoseltamab Demonstrates High Efficacy, Low Toxicity: Paula Rodríguez-Otero, MD, PhD

The phase 2 LINKER-SMM1 trial (NCT05955508) is investigating the safety and efficacy of linvoseltamab in patients with high-risk smoldering multiple myeloma. Top results from this investigation so far include a 100% response rate after 1 cycle of treatment, 70% of patients achieving a response, no cases of ICANS (immune effector cell–associated neurotoxicity syndrome), and 3 cases of grade 1 cytokine release syndrome (CRS) among the 24 patients so far treated.

Paula Rodríguez-Otero, MD, PhD, Cancer Center Clínica Universidad de Navarra (University of Navarra), Pamplona, Spain, presented this research, “Safety and Efficacy of Linvoseltamab (LINVO) in Patients (Pts) With High-Risk Smoldering Multiple Myeloma (HR-SMM): First Results From the Phase 2 LINKER-SMM1 Trial,” at the 22nd International Myeloma Society annual meeting.

Revisit part 1 of this interview, where Rodríguez-Otero discusses how linvoseltamab helps to prevent myeloma progression, before reading on to learn more about the bispecific T-cell engager safety profile.

This transcript has been lightly edited for clarity; captions were auto-generated.

Transcript

What key factors may have contributed to the high overall response rate observed after 1 cycle of treatment?

We know linvoseltamab is a very active drug, and already the overall response rate is really high also in the triple-class-exposed setting, with over 70% of the patients achieving a response. Our hypothesis is that indeed because here we do see, the disease is being treated early, eventually with less clonal heterogeneity, not resistant disease, because these are all treatment-naive patients and also with a more potent immune system, so that will probably explain the higher overall response rate.

How do the safety profiles compare between patients with early-stage and relapsed/refractory disease?

The safety profile seems more favorable. We haven't seen any ICANS so far in these 24 patients treated. Infections are common, but overall less severe. We do see a very limited incidence of severe infection; only 3 patients had grade 3 events, and also the majority of the CRS events were grade 1. Also, it's important to highlight that the step- up dose was different compared to the step-up dose used in the relapsed settings, so that also may have contributed to the lower ICANS and the lower CRS.

What criteria are most important for selecting high-risk patients for early treatment with linvoseltamab?

This is a very important question. Currently we have, I would say that the consensus criteria is the 2-20-20 International Myeloma Working Group criteria that defines high-risk smoldering for patients that have serum protein over 2 g/dL, free light chains over 20, and more than 20% infiltration of clonal plasma cells in the marrow. That is, I would say, the recent consensus of the International Group. Definitely, these criteria will evolve as we incorporate more modern risk features, such as the presence of circulating plasma cells, functional imaging, genomics. All this will evolve and eventually in the future, we will use more refined criteria to define high-risk smoldering.