Dr Richter on the FDA Approval of Linvoseltamab for R/R Multiple Myeloma

"Having more tools…allows us to personalize the therapy for an individual [with multiple myeloma]."

Joshua Richter, MD, an associate professor of medicine in the Division of Hematology and Medical Oncology at the Tisch Cancer Institute and director of Multiple Myeloma at the Blavatnik Family- Chelsea Medical Center at Mount Sinai, discussed the implications of the FDA’s accelerated approval of linvoseltamab-gcpt (Lynozyfic) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

The FDA’s July 2, 2025, approval was supported by data from the phase 1/2 LINKER-MM1 trial (NCT03761108), which demonstrated a confirmed objective response rate (ORR) of 70% (95% CI, 59%-80%), including a complete response (CR) rate of 45% (95% CI, 34%-57%), a very good partial response (VGPR) rate of 15%, and PR rate of 5%. The median time to first response was 0.95 months (range, 0.5-6), and the median duration of response (DOR) was not reached (95% CI, 12-not evaluable) at the time of data cutoff. The estimated 9- and 12-month DOR rates were 89% and 72%, respectively, with follow-up of 11.3 months.

The approved regimen utilizes a step-up dosing strategy to mitigate cytokine release syndrome, Richter explained, beginning with 5 mg on cycle 1, day 1; 25 mg on day 8; and the target dose of 200 mg on day 15. This step-up dosing, which is part of the recommended dose of the agent, is followed by 200-mg doses given weekly for 10 total doses, then 200 mg once every 2 weeks. Notably, in patients who achieve a VGPR or better at or after week 24 who also received at least 17 200-mg doses, linvoseltamab can be given at 200 mg once every 4 weeks. According to Richter, pharmacokinetic and pharmacodynamic data indicated that the 200-mg dose supported extended monthly dosing without compromising efficacy. This dose was studied in over 100 patients in the trial, including individuals with high-risk features, he said, noting that more than one-third of patients treated had high-risk cytogenetic abnormalities, and over one-quarter had penta-refractory disease.

Given the growing landscape of treatment options in the multiple myeloma field, Richter explained that each patient’s treatment journey needs to be individualized. Linvoseltamab now represents another option for some patients in later lines of treatment, he concluded.