Linvoseltamab in Patients With Relapsed/Refractory Multiple Myeloma in the LINKER-MM1 Study: Longer Follow-Up and Subgroup Analyses

Background: Linvoseltamab, a BCMA × CD3 bispecific antibody, demonstrated durable efficacy and generally manageable safety in patients with relapsed/refractory multiple myeloma (RRMM) in the LINKER-MM1 study (NCT03761108). Methods: We conducted an updated analysis with a longer median follow-up of 21.3 months for 117 patients from LINKER-MM1 who received linvoseltamab 200 mg, including response data in high-risk subgroups. Results: As of July 23, 2024 (data cutoff), the objective response rate (ORR) was 71% (complete response or better [≥CR], 52%), with median duration of response of 29.4 months. Median progression-free survival was not reached, and median overall survival was 31.4 months. Minimal residual disease negativity (10⁻⁵ threshold) was achieved in 94% of evaluable patients with ≥CR. High response rates were observed across subgroups defined by baseline patient characteristics (age and race) and treatment history (eg, penta-refractory status). Response rates and survival outcomes were favorable in patients with markers of high disease burden (elevated % bone marrow plasma cells or soluble BCMA) or difficult-to-treat RRMM (including extramedullary plasmacytoma, International Staging System stage 3, and high-risk cytogenetic status); ORR was ≥50% in all subgroups assessed. The most common treatment-emergent adverse events were cytokine release syndrome (46%; Grade 3, 1%; most events occurred during step-up dosing) and neutropenia (44%; Grade ≥3, 43%). Infections were reported in 75% of patients (Grade ≥3, 48%), with the rate decreasing after 6 months of treatment. Conclusions: Long-term treatment with linvoseltamab 200 mg provided deep and durable responses, with no new safety signals, and thus represents an effective therapeutic option in RRMM.