Dr Rodriguez-Otero on Data for Linvoseltamab in High-Risk Smoldering Myeloma

“The efficacy of linvoseltamab in this population is quite remarkable. [In the] 19 out of the 24 patients that were presented [at IMS 2025 who] are evaluable for response…the overall response rate was 100%.”

Paula Rodriguez-Otero, MD, a consultant hematologist and deputy professor at Clínica Universidad de Navarra, discussed safety and efficacy findings with linvoseltamab-gcpt (Lynozyfic) in patients with high-risk smoldering multiple myeloma.

During the 22nd Annual International Myeloma Society Meeting and Exposition, Rodriguez-Otero presented the first results from the phase 2 LINKER-SMM1 trial (NCT05932680), which evaluated linvoseltamab in this high-risk precursor population.

The safety profile of linvoseltamab in patients with high-risk smoldering multiple myeloma appeared more favorable than that observed in relapsed/refractory multiple myeloma. Rates of grade 3 or higher treatment-emergent adverse effects (TEAEs), including infections, were lower; additionally, no immune effector cell–associated neurotoxicity syndrome (ICANS), treatment discontinuations, or treatment-related deaths were reported. Cytokine release syndrome (CRS) occurred in 42% of patients, all at grade 1 or 2 effects. Infections were reported in 79% of patients, but the rate of grade 3 or higher infections was 12.5%.

Among the efficacy-evaluable population (n = 19), the overall response rate (ORR) was 100% at a median follow-up of 3.9 months. The rate of very good partial response (VGPR) or better was 73.7%, and the complete response (CR) or better rate was 36.8%. In the safety run-in portion (n = 6; median follow-up 12.7 months), 83.3% of patients achieved CR or better, suggesting that responses with linvoseltamab deepened over time. Minimal residual disease (MRD) assessments were performed in patients who achieved VGPR or better. Of the 12 patients with evaluable samples, all achieved MRD negativity at 10-6 sensitivity. All responses were ongoing at the time of data cutoff.

Rodriguez-Otero noted that these preliminary findings provide proof-of-concept for targeting BCMA in high-risk smoldering multiple myeloma, a population with limited treatment options and high progression rates. The observed efficacy, combined with deep MRD negativity, supports continued evaluation of linvoseltamab in larger patient cohorts with longer follow-up to establish durability and survival outcomes.