Linvoseltamab for RR Multiple Myeloma: Deep, Durable Responses at 14-Month Follow-Up (LINKER-MM1)

Linvoseltamab in Patients with Relapsed/Refractory Multiple Myeloma in the LINKER-MM1 Study: Depth and Durability of Response at 14-Month Median Follow-Up
Summary:
The study evaluated the efficacy and safety of linvoseltamab, a B-cell maturation antigen × CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM). The results showed that linvoseltamab induced high rates of deep and durable responses in RRMM patients, including those in high-risk subgroups. The median follow-up duration was 11.1 months, and the objective response rate (ORR) was 71%, with a very good partial response (VGPR) rate of 62% and a complete response (CR) rate of 46%. The median duration of response (DOR) was not reached, and the probability of maintaining response at 12 months was 78% for all responders and 92% for patients with CR. The median progression-free survival (PFS) and overall survival (OS) were not reached, with a 12-month probability of PFS and OS of 69% and 75%, respectively, for all patients receiving 200 mg. The study also demonstrated efficacy in high-risk subgroups, such as patients with plasmacytomas and high cytogenetic risk. Adverse events included cytokine release syndrome, neutropenia, and anemia, with infections reported in 73% of patients. However, a reduction in infection frequency and severity was observed after 6 months of treatment. Overall, linvoseltamab showed promising results in RRMM patients, and further long-term data will be presented to establish its value in the treatment of RRMM.
Key Points:
• Linvoseltamab, a B-cell maturation antigen × CD3 bispecific antibody, was evaluated in patients with relapsed/refractory multiple myeloma (RRMM).
• The study included Phase 1/2 patients who were triple-class exposed or triple-class refractory.
• Patients received intravenous linvoseltamab once weekly for 14 weeks, followed by once every 2 weeks.
• The primary endpoint was objective response rate (ORR), and secondary endpoints included safety, duration of response (DOR), progression-free survival (PFS), and overall survival (OS).
• The median follow-up duration was 11.1 months for the 117 patients enrolled in the 200 mg dosing cohorts.
• Linvoseltamab treatment showed an ORR of 71%, with a very good partial response (VGPR) rate of 62% and a complete response (CR) rate of 46%.
• The median duration of response (DOR) was not reached, and the probability of maintaining response at 12 months was 78% for all responders and 92% for patients with CR.
• The median progression-free survival (PFS) and overall survival (OS) were not reached for all patients receiving 200 mg.
• High response rates and deep responses were observed in high-risk subgroups, including patients with plasmacytomas and high cytogenetic risk.
• In patients aged ≥75 years, the ORR was 71%, with 52% achieving CR. In patients identifying as Black or African American, the ORR was 85%, with 35% achieving CR.
• The most common treatment-emergent adverse event was cytokine release syndrome (46% of patients), followed by neutropenia and anemia.
• Infections were reported in 73% of patients, but a reduction in frequency and severity was observed after 6 months of treatment.
• Patients with CR had no Grade 5 infections.
• Long-term data will be presented to establish the value of linvoseltamab in the treatment of RRMM.
Authors:
Suzanne Lentzsch, Naresh Bumma, Hans Lee, Attaya Suvannasankha, James E. Hoffman, Joshua Richter, Madhav Dhodapkar, Joseph J. Maly, Rebecca Silbermann, Chang-Ki Min, Matthew J. Pianko, Marie-Christiane Vekemans, Michelle DeVeaux, Dhruti Chokshi, Anita Boyapati, Cristina Karen Rodriguez Lorenc, Glenn Kroog, Yariv Houvras, Sundar Jagannath
EHA Abstract: S212