Linvoseltamab demonstrated strong early activity and a more favorable safety profile in patients with high-risk smoldering multiple myeloma (HR-SMM) compared with relapsed or refractory MM, according to first reported results from the phase 2 LINKER-SMM1 trial.
The study was led by Paula Rodríguez-Otero, MD, PhD, a consultant hematologist at Clínica Universidad de Navarra, who presented the results during an oral abstract session on September 19, 2025 at the International Myeloma Society Annual Meeting.
The phase 2 LINKER-SMM1 trial evaluated the BCMA×CD3 bispecific antibody as an early intervention for HR-SMM across multiple Spanish centers.
Safety profile results
Dr. Rodríguez-Otero reported that linvoseltamab showed a favorable safety profile in this patient group, including the following:
- Cytokine release syndrome was reported in 42% of patients, including grade 1–2 events. There were no cases of ICANS.
- Infections were reported in 79% of patients, with only three (12.5%) grade 3 events (one COVID-19, one salmonella gastroenteritis, one staphylococcal bacteremia.
- The investigators reported no treatment discontinuations or treatment-related deaths.
Preliminary efficacy was also positive. Among the 19 evaluable patients, the overall response rate (ORR) was 100%, with 73.7%% achieving ≥VGPR. All 12 patients with available samples were MRD-negative (10⁻⁶ sensitivity), and responses deepened over time, she reported.
“These early data suggest that by intervening in high-risk smoldering myeloma, when the immune system is more intact, we may significantly delay or even prevent progression to active disease,” Dr. Rodríguez-Otero said.
Funding for the study was provided by Regeneron.
Reference
Rodriguez-Otero P. 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. Abstract OA-68. Presented at the 2025 International Myeloma Society Annual Meeting; September 17-20; Toronto, Canada.
