Linvoseltamab Approved for R/R Multiple Myeloma

The FDA has granted accelerated approval to linvoseltamab (Lynozyfic, Regeneron) for relapsed or refractory multiple myeloma (MM) after at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti‑CD38 monoclonal antibody. 

The bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager joins two others already on the US market for the same indication, teclistamab (Tecvayli, Johnson & Johnson) and elranatamab (Elrexfio, Pfizer). The approval of linvoseltamab was based on 80 patients treated with 200 mg intravenously in the phase 1/2 LINKER-MM1 trial who had received at least 4 prior lines of therapy but not a previous BCMA-directed bispecific antibody. 

The objective response rate was 70%, with 45% of patients achieving a complete response. The estimated duration of response was 89% at 9 months and 72% at 12 months. 

The outcomes are among the best reported so far for a bispecific antibody in heavily pretreated MM. Linvoseltamab is also the only one that can be dosed every 4 weeks in patients who are doing well after at least 24 weeks of treatment, according to a Regeneron press release. 

Because of that, “we believe Lynozyfic is poised to potentially become a new standard of care for multiple myeloma. Furthermore, given the strength of the data, we are rapidly advancing our broad clinical development program for Lynozyfic — exploring its use in earlier lines of therapy as monotherapy and in novel combinations,” a company executive said in the release.

Regeneron has a phase 3 trial in the works to confirm clinical benefit. It is also testing subcutaneous administration, which is the route of administration for teclistamab and elranatamab. 

Like both of those agents, linvoseltamab carries a boxed warning of life-threatening cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS). All three agents are available only through a Risk Evaluation and Mitigation Strategy program.

The rate of CRS in LINKER-MM1 was 46%, with grade 3 CRS occurring in less than 1% of patients. ICANS occurred in 54%, with grade 3/4 neurologic toxicity in 8%.

Other warnings and precautions include infections, neutropenia, hepatotoxicity, and embryo-fetal toxicity. 

Linvoseltamab is administered with an initial step-up dosing regimen followed by the full 200 mg dose weekly. At week 14, patients transition to every 2-week dosing. Patients who achieve and maintain a very good partial response or better shift to monthly dosing after 24 weeks. 

Linvoseltamab requires a 24-hour hospitalization for safety after the first and second step-up doses. 

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: [email protected]