teclistamab — Drug Monograph

Teclistamab (Tecvayli) — BCMA Bispecific for Relapsed/Refractory Myeloma

Teclistamab (Tecvayli) is a BCMA-directed, CD3-engaging bispecific antibody for relapsed or refractory multiple myeloma. It bridges B-cell maturation antigen (BCMA) on malignant plasma cells with CD3 on T lymphocytes, redirecting T-cell cytotoxicity independent of MHC presentation. Because T-cell activation can cause cytokine release syndrome (CRS) and ICANS, teclistamab uses a subcutaneous step-up schedule and is delivered under a REMS program. This monograph covers teclistamab indications in relapsed/refractory multiple myeloma, the BCMA binding mechanism, step-up dosing, mandatory initial hospitalization, and infection prophylaxis with immunoglobulin support for hypogammaglobulinemia.

Indications (FDA / NCCN)

• Relapsed or refractory multiple myeloma after ≥4 prior lines (including a PI, an IMiD, and an anti-CD38 antibody)
• Accelerated approval based on MajesTEC-1
• BCMA-targeted bispecific; part of the Tecvayli REMS program

Dosing

• Subcutaneous step-up: 0.06 (Day 1) → 0.3 (Day 4) → 1.5 mg/kg (Day 7 / Week 2)
• Then 1.5 mg/kg SC weekly
• After ≥6 months with ≥PR: may transition to 3 mg/kg every 2 weeks
• Premedicate (dexamethasone, antihistamine, acetaminophen) for first 3 doses

Monitoring

• Hospitalize ≥48 h after step-up Doses 1 and 2 for CRS/ICANS
• Serum IgG every 3 months; consider IVIG if IgG <400 mg/dL
• Infection prophylaxis (PJP, HSV/VZV antiviral)
• CBC with differential; neurologic assessment for ICANS

Brand names: Tecvayli

Drug class: Monoclonal Antibody

Mechanism of Action

Teclistamab is a humanized IgG4-PAA bispecific antibody that bridges BCMA (B-cell maturation antigen) on malignant plasma cells with CD3ε on T lymphocytes, redirecting T-cell cytotoxicity toward BCMA-expressing myeloma cells. BCMA is a TNF receptor superfamily member selectively expressed on mature B cells and plasma cells, and is upregulated on malignant plasma cells. Dual binding creates an immunological synapse independent of MHC-peptide-TCR interaction, triggering granzyme/perforin-mediated lysis of target cells. The IgG4 backbone with stabilizing mutations reduces Fc effector function…

FDA Indications

• Relapsed or refractory multiple myeloma after ≥4 prior lines of therapy including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody (October 2022, accelerated approval; MajesTEC-1 trial)

Common Side Effects

• CRS (~72%, predominantly Grade 1–2)
• Neutropenia (~71%)
• Anemia (~55%)
• Thrombocytopenia (~40%)
• Fatigue (~36%)
• Pyrexia (~35%)
• Upper respiratory tract infection (~34%)
• Injection site reactions (~23%)
• Diarrhea (~23%)
• Nausea (~19%)
• Hypogammaglobulinemia (~16%)
• Headache (~14%)
• Musculoskeletal pain (~13%)

Clinical Pearl

Teclistamab was the first BCMA×CD3 bispecific antibody approved for myeloma and established the feasibility of SC bispecific antibody therapy with outpatient administration after inpatient step-up dosing. The near-universal CRS incidence (~72%) reflects the high immunological potency of the BCMA×CD3 bridge; however, the vast majority of CRS events are Grade 1–2 and resolve with supportive care. Profound neutropenia is nearly universal and often requires G-CSF support; patients should be…

Related Therapies & Mechanisms

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