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 14.3 months, and the objective response rate (ORR) was 71%, with a very good partial response (VGPR) rate of 63% and a complete response (CR) rate of 50%. The median duration of response (DoR) was 29.4 months, and the probability of maintaining response at 12 months was 81% for all responders 200 mg patients and 95% for 200 mg patients with a CR or better. The median progression-free survival (PFS) was not reached, with a 12-month probability of PFS at 70% for all patients receiving 200 mg. The median overall survival (OS) was 31.4 months, and the probability of survival at 12 months was 75% for all 200 mg patients and 100% for 200 mg patients with a CR or better. The study also demonstrated efficacy in prespecified subgroups, such as patients with extramedullary plasmacytomas and high-risk cytogenetics risk. Adverse events included cytokine release syndrome, neutropenia, and anemia, with infections reported in 74% of patients. However, a reduction in infection frequency and severity was observed after 6 months of treatment.
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 14.3 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 63% and a complete response (CR) rate of 50%.
The median duration of response (DoR) was 29.4 months, and the probability of maintaining response at 12 months was 81% for all 200 mg patients and 95% for patients with a CR or better.
The median progression-free survival (PFS) was not reached, with a 12-month probability of PFS at 70% for all patients receiving 200 mg.
The median overall survival (OS) was 31.4 months, and the probability of survival at 12 months was 75% for all 200 mg patients and 100% for 200 mg patients with a CR or better.
High response rates and deep responses were observed prespecified subgroups, including patients with extramedullary plasmacytomas and high-risk cytogenetics.
In patients aged ≥75 years, the ORR was 71%, with 55% achieving CR. In patients identifying as Black or African American, the ORR was 85%, with 45% 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 74% 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