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

Suzanne Lentzsch, MD, PhD, professor, medicine, director, Multiple Myeloma and Amyloidosis Program, Columbia University Herbert Irving Comprehensive Cancer Center, discusses safety data presented at the 2024 EHA Congress from the phase 1/2 LINKER-MM1 study (NCT03761108), which evaluated linvoseltamab (REGN5458) in patients with relapsed/refractory multiple myeloma.

In terms of safety, the most common adverse effects (AEs) observed were neutropenia and anemia, both of which are known AEs associated with bispecific antibodies, Lentzsch begins, adding that these hematologic AEs are consistent with those typically observed in this patient population. In total, 41.9% of patients had grade 3/4 neutropenia, and 30.8% of patients had grade 3/4 anemia. Serious AEs were reported in approximately 46% of patients; however, the majority of these were grade 1 or 2 in severity. Approximately 1% of patients experienced grade 3 serious AEs, and no grade 4 AEs were reported.

Infections were a notable concern, with a total of 74.4% of patients experiencing infections, with 35.9% of patients developing grade 3 or 4 infections, which often necessitated interventions such as intravenous antibiotics or hospitalization, Lentzsch reports. However, Lentzsch explains that a significant reduction in infection rates occurred over time. During the first 3 months of treatment, the rate of infections was approximately 20%, but this rate decreased to approximately 6% after 1 year. These findings indicate that the risk of infections may diminish with ongoing treatment, especially with the use of supportive care measures like prophylactic antibiotics and intravenous immunoglobulin.

Overall, linvoseltamab was associated with a tolerable safety profile in this heavily pretreated patient population, according to Lentzsch. Despite the notable occurrence of infections and hematologic toxicities, these AEs were generally manageable, particularly over the longer term, she notes.

The reduction in infection rates and the absence of severe, persistent toxicities with linvoseltamab therapy support the continued evaluation of this agent as a therapeutic option for patients with relapsed/refractory multiple myeloma, as further investigation is warranted to fully establish its safety and efficacy in this setting, Lentzsch concludes.

Notably, in August 2024, the FDA issued a complete response letter to the biologics license application seeking the approval of linvoseltamab for the treatment of patients with relapsed/refractory multiple myeloma. The drug’s developer cited issues with a pre-approval inspection at a third-party manufacturer as the sole approvability issues, and the FDA is expected to reinspect the facility in the future.