Paula Rodriguez Otero, MD, PhD, Hematologist at the University of Navarra, discusses results from the LINKER-SMM1 trial in patients with high-risk smoldering multiple myeloma (HR-SMM).
HR-SMM is an asymptomatic clonal plasma cell disorder characterized by a high risk of progression to multiple myeloma. The typical age of diagnosis is 50 to 70 years. Due to its asymptomatic nature, diagnosis usually follows discovery of M protein in laboratory testing. Early intervention may have the potential to delay or prevent progression to active multiple myeloma.
Data from the LINKER-SMM1 clinical trial was recently presented at the International Myeloma Society 2025 meeting. The LINKER-SMM1 (NCT05955508) study is a phase 2, open-label trial evaluating the safety and efficacy of linvoseltamab in patients with HR-SMM. Linvoseltamab is a BCMAxCD3 bispecific antibody approved for triple-class exposed relapsed/refractory multiple myeloma after 4 or more prior lines of therapy.
Part 1 of the study looked at the safety of linvoseltamab in six patients. Primary endpoints included frequency of adverse events of special interest, and frequency and severity of treatment-emergent adverse events (TEAE). Part 2 of the study is ongoing with 24 patients enrolled as of May 28, 2025. Primary endpoints include complete response rate and MRD negativity at 12 and 24 months. Key secondary endpoints of both parts include overall response rate, MRD negativity rate, and duration of response.
In part 1, no safety concerns were identified. 92% of patients experienced 1 or more TEAE and 38% experienced a grade 3 or higher TEAE. Neutropenia was the only grade 3 or higher hematologic toxicity. Infections occurred in 79% of patients and consisted mostly of low-grade respiratory tract infections. However, treatment-related grade 3 infections were reported in 2 patients with Salmonella gastroenteritis and Staphylococcus epidermidis bacteremia, which were quickly resolved with antibiotics. Ig replacement was given to 95% of patients who received 1 or more cycles of therapy. CRS occurred in 42% but no ICANS were observed.
Following one or more cycles of linvoseltamab, overall response rate was 100%. Among part 1 patients with longer follow-up, 100% achieved ≥VGPR and 100% achieved MRD negativity at 10-6. All responses were ongoing at data cutoff.
To learn more about HR-SMM and other rare cancers, visit https://checkrare.com/diseases/cancers/
Tags: hematology, cancer, drug development