Dr Jagannath on the Safety of Linvoseltamab in Relapsed/Refractory Multiple Myeloma

Sundar Jagannath, MBBS, director, Center of Excellence for Multiple Myeloma, professor, medicine (hematology and medical oncology), The Tisch Cancer Institute, Mount Sinai, discusses the safety profile of linvoseltamab (REGN5458) in patients with relapsed/refractory multiple myeloma.

During the 2024 AACR Annual Meeting, findings from the phase 1/2 LINKER-MM1 trial (NCT03761108) were shared, including safety considerations for the use of the agent. The safety data shed light on key aspects of BCMA-directed bispecific antibody therapy, Jagannath begins, saying one notable consideration with this class of medications is the risk of cytokine release syndrome. Additionally, the trial revealed that low blood counts, particularly neutropenia and anemia, were common adverse effects that require careful monitoring. The depletion of normal plasma cells poses a risk of infection due to reduced antibody production in response to pathogens, he explains.

Neutropenia and anemia were observed during the study, and 73% of patients experienced infections of any grade, with 34% of patients experiencing grade 3/4 infections, Jagannath reports. The trial involved initial weekly dosing for the first 14 weeks, then biweekly dosing from weeks 16 to 23, followed by monthly dosing at 24 weeks for patients achieving very good partial response (VGPR) or better.

The study’s infection rate analysis demonstrated a well-structured design, he says. Infections were more frequent during the first 6 months of treatment, with any-grade infection rates decreasing over time, he expands. Notably, the rate of grade 3/4 infections, which is a significant concern, decreased between the 0-to-3-month and 6-to-9-month periods, reflecting a trend toward improved infection management and decreased severity with continued treatment, Jagannath emphasizes. The treatment responses observed in the trial, including a median time to partial response or better of 4 weeks (range, 0.5-6.3) and a median time to VGPR or better of 2.6 months (range, 0.7-13.1), contributed to the reduction in infection rates over time. The study’s proactive approach to infection management included allowing patients to receive prophylactic antibiotics, he concludes.