linvoseltamab — Drug Monograph

Linvoseltamab (Lynozyfic) — BCMA Bispecific for Relapsed/Refractory Myeloma

Linvoseltamab (Lynozyfic) is a BCMA-directed, CD3-engaging bispecific antibody for relapsed or refractory multiple myeloma. It binds B-cell maturation antigen (BCMA) on malignant plasma cells and CD3 on T lymphocytes, forming an immunological synapse that redirects T-cell cytotoxicity in an MHC-independent manner. Its intravenous route allows precise dose titration and rapid infusion adjustment, and after response patients may transition to every-4-week maintenance. Because T-cell activation can trigger cytokine release syndrome (CRS), it uses a step-up schedule. This monograph covers linvoseltamab indications in relapsed/refractory multiple myeloma, the BCMA binding mechanism, step-up dosing, and CRS and infection management.

Indications (FDA / NCCN)

• Relapsed or refractory multiple myeloma after ≥3 prior lines (including a PI, an IMiD, and an anti-CD38 antibody)
• Accelerated approval based on LINKER-MM1
• BCMA-directed bispecific; prior anti-BCMA therapy may reduce efficacy

Dosing

• IV step-up: 5 mg (Day 1) → 25 mg (Day 8) → 200 mg (Day 15)
• Then 200 mg IV weekly from Week 3; may transition to every 4 weeks after response
• Premedicate (corticosteroid, antihistamine, antipyretic) before each step-up dose
• Infuse Dose 1 over 4 h, Dose 2 over 2 h, later doses over 1 h if tolerated

Monitoring

• Hospitalization during step-up strongly recommended; monitor ≥2 h post-infusion for first 3 doses
• CRS signs/symptoms (~46%, mostly Grade 1–2)
• Infection prophylaxis and regular IgG surveillance
• CBC; watch for secondary T-cell malignancies (BCMA class concern)

Brand names: Lynozyfic

Drug class: Monoclonal Antibody

Mechanism of Action

Linvoseltamab is a humanized IgG4 bispecific antibody that binds BCMA (B-cell maturation antigen) on malignant plasma cells and CD3ε on T lymphocytes, forming an immunological synapse that redirects T-cell cytotoxicity to lyse BCMA-expressing myeloma cells. BCMA engagement coupled with CD3 crosslinking activates T cells in an MHC-independent manner, inducing perforin/granzyme-mediated and Fas/FasL-mediated apoptosis of target cells. The IgG4 isotype minimizes Fc receptor-mediated off-target effector functions, and the formulation supports an intravenous route facilitating dose titration and…

FDA Indications

• Relapsed or refractory multiple myeloma after ≥3 prior lines of therapy including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody (July 2025, accelerated approval; LINKER-MM1 trial)

Common Side Effects

• CRS (~46%, predominantly Grade 1–2)
• Neutropenia (~57%)
• Anemia (~49%)
• Fatigue (~38%)
• Thrombocytopenia (~34%)
• Pyrexia (~28%)
• Upper respiratory tract infection (~26%)
• Diarrhea (~22%)
• Nausea (~20%)
• Hypogammaglobulinemia (~19%)
• Cough (~16%)
• Headache (~14%)
• Infusion-related reactions (~12%)

Clinical Pearl

Linvoseltamab's IV administration differentiates it from the SC BCMA bispecifics and allows precise dose titration and immediate infusion rate adjustments in the event of infusion reactions. The Q4W maintenance dosing option after achieving response substantially reduces treatment burden and clinic visits for responding patients, a meaningful quality-of-life consideration in the heavily pre-treated myeloma population. As with other BCMA-directed agents, prior exposure to anti-BCMA therapies…

Related Therapies & Mechanisms

• Daratumumab (Darzalex) — Monoclonal Antibody · Myeloma
• Elotuzumab (Empliciti) — Monoclonal Antibody · Myeloma
• Elranatamab (Elrexfio) — Monoclonal Antibody · Myeloma
• Isatuximab (Sarclisa) — Monoclonal Antibody · Myeloma