Dr Jagannath on the Mechanism of Action of Linvoseltamab in R/R Multiple Myeloma

Sundar Jagannath, MBBS, director, Center of Excellence for Multiple Myeloma, professor of medicine (hematology and medical oncology), The Tisch Cancer Institute, Mount Sinai, discusses the mechanism of action of linvoseltamab (REGN5458) in patients with relapsed/refractory multiple myeloma and how the dosing schedule of this agent reflects its tolerability.

Linvoseltamab is a bispecific antibody that binds to both BCMA and CD3, bringing the patient’s T cells in close proximity to cancer cells and promoting their destruction, Jagannath says. Since 2 BCMA-directed bispecific antibodies are already FDA approved for patients with multiple myeloma, oncologists are already familiar with the efficacy of these agents, Jagannath notes. Teclistamab-cqyv (Tecvayli) was approved in October of 2022 for patients with relapsed/refractory multiple myeloma who had received at least 4 prior lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD), and an anti-CD38 monoclonal antibody. Elranatamab-bcmm (Elrexfio) was approved for the same indication in August of 2023. The phase 1/2 LINKER-MM1 trial (NCT03761108) is evaluating linvoseltamab in patients with multiple myeloma who have received at least 3 prior lines of therapy, including a PI, an IMiD, and an anti-CD38 monoclonal antibody, or those who had double- or triple-class– refractory disease.

Linvoseltamab is a fully humanized antibody, which distinguishes it from other bispecific antibodies, Jagannath explains. Furthermore, patients only need to be admitted to the hospital for 2 24-hour infusions of linvoseltamab during the weekly step-up dosing phase, since the agent demonstrated a tolerable adverse effect profile in LINKER-MM1, Jagannath emphasizes. During step-up dosing, patients receive 5 mg of linvoseltamab on day 1 and 25 mg of the agent on day 8. Beginning at week 3, when patients receive the agent at 200 mg once a week, they do not need to be admitted to the hospital. Furthermore, instances of cytokine release syndrome associated with linvoseltamab have been manageable, according to Jagannath. Therefore, this agent can be administered mostly in outpatient settings, with minimal hospitalization required, Jagannath says.