Linvoseltamab-gcpt (Lynozyfic) is a bispecific BCMA-directed CD3 T-cell engager (a recombinant human IgG4 antibody) indicated for adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
It is a BCMA-CD3-directed bispecific antibody.
Bridging Cells: One arm attaches to B-cell maturation antigen (BCMA) on myeloma cells.
The other arm attaches to CD3 on T-cells.Immune Response: It brings the T-cell close to the cancer cell to trigger cell death.
It binds CD3 on T-cells and BCMA on myeloma cells, activating T-cells to release proinflammatory cytokines and lyse myeloma cells.
Approval for patients who received at least four prior lines of therapy.
Begins with initial step-up doses (such as 5 mg and 25 mg) before reaching the target dose.
Maintenance: Administered intravenously at 200 mg weekly, transitioning to biweekly or every four weeks based on patient response.
Dosing (IV only, after dilution in 0.9% sodium chloride): A step-up schedule of 5 mg, then 25 mg, then 200 mg, followed by 200 mg weekly for 10 doses, then 200 mg every 2 weeks.
In patients who achieve and maintain VGPR or better at/after week 24 and have received at least 17 doses of 200 mg, dosing decreases to 200 mg every 4 weeks.
Premedicate to reduce CRS and infusion-related reactions, and hospitalize patients for 24 hours after each of the first two step-up doses.
Boxed warning — CRS and neurologic toxicity (including ICANS):
CRS occurred in 46% of patients at the recommended dose (Grade 1 in 35%, Grade 2 in 10%, Grade 3 in 0.9%).
Most CRS (38%) followed step-up dose 1; median time to onset was 11 hours after infusion with a median duration of 15 hours; recurrent CRS occurred in 20%.
Manifestations include pyrexia, chills, hypoxia, tachycardia, and hypotension.
Neurologic toxicity including ICANS occurred in 54%, with Grade 3–4 in 8%.
Because of these risks, linvoseltamab is available only through the Lynozyfic REMS.
Other warnings and precautions: serious/fatal infections, neutropenia, hepatotoxicity, infusion-related reactions (9%), and embryo-fetal toxicity.
Pivotal efficacy In the phase I/II first-in-human trial, among the 117 patients treated at the 200 mg dose (median age 70, 39% high-risk cytogenetics, 28% penta-refractory), the overall response rate was 71%, with 50% achieving ≥complete response, and a median duration of response of 29.4 months at a median follow-up of 14.3 months.
The FDA-labeled efficacy population (80 patients with ≥4 prior lines) had an ORR of 70%, with DOR of 89% at 9 months and 72% at 12 months.
The most common toxicities at 200 mg were CRS, neutropenia (Grade 3–4 ~42%), anemia (Grade 3 ~31%), and infections (74%, declining in frequency over time).
The NCCN Multiple Myeloma guidelines list linvoseltamab-gcpt as a preferred bispecific antibody option for relapsed/refractory disease after at least four prior therapies (including an anti-CD38 antibody, a PI, and an IMiD), alongside elranatamab, talquetamab, and teclistamab; prophylactic tocilizumab may be considered before the first dose to reduce CRS risk.
The 2026 ASCO guidelines note that these bispecific agents all produce impressive efficacy in heavily pretreated patients but carry unique toxicities, and—absent head-to-head comparisons—no preferred agent can be recommended.
EHA–EMN guidelines similarly include linvoseltamab as an option (level II, B) for triple-class refractory disease.
Linvoseltamab combined with carfilzomib (LINKER-MM2) produced high response rates in RRMM, with an ORR of 91% at the 100 mg dose level and 100% at 150 mg, and CRS in 61% (none ≥Grade 3), though follow-up remains short and enrollment at the 200 mg dose is ongoing.