LINKER-MM1 Trial Design and the Clinical Rationale Behind Linvoseltamab

Drs Paul Richardson and Hans Lee walk through the pivotal LINKER-MM1 trial that supported the July 2025 approval of linvoseltamab for patients with relapsed or refractory multiple myeloma after multiple prior lines of therapy. Dr Lee outlines the phase 1/2 study design, key eligibility criteria, and the rationale behind evaluating both 50-mg and 200-mg dosing cohorts, emphasizing the careful dose optimization process undertaken with regulatory guidance. The discussion highlights the unique step-up dosing schedule and planned de-escalation strategy, including the transition to less frequent dosing for patients achieving deep responses. The faculty also reflect on how closely the LINKER-MM1 population mirrors real-world practice, including older adults, patients with high-risk cytogenetics, and those with heavy disease burden. Together, they review emerging efficacy signals, depth and durability of response, and practical considerations such as tolerability, administration route, and early safety management, setting the stage for understanding how linvoseltamab differentiates itself among BCMA-directed bispecific therapies.