elranatamab — Drug Monograph

Elranatamab (Elrexfio) — BCMA Bispecific for Relapsed/Refractory Myeloma

Elranatamab (Elrexfio) is a BCMA-directed bispecific antibody for relapsed or refractory multiple myeloma. It simultaneously engages B-cell maturation antigen (BCMA) on malignant plasma cells and CD3 on T cells, redirecting cytotoxic T lymphocytes to kill BCMA-expressing myeloma cells independent of MHC presentation. Because T-cell activation can trigger cytokine release syndrome (CRS), elranatamab uses a subcutaneous step-up dosing sequence to mitigate CRS before weekly maintenance. This monograph covers elranatamab indications in relapsed/refractory multiple myeloma, the BCMA bispecific mechanism, the step-up dosing schedule, and CRS mitigation and monitoring.

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 MagnetisMM-3
• BCMA-directed bispecific — prior anti-BCMA therapy may reduce efficacy

Dosing

• Subcutaneous step-up: 12 mg (Wk 1 Day 1) → 32 mg (Wk 1 Day 4) → 76 mg (Wk 2)
• Then 76 mg SC weekly (Weeks 3–24)
• After Week 24 with adequate response: 76 mg SC every 2 weeks
• Premedicate (dexamethasone, antihistamine, antipyretic) before first 3 doses

Monitoring

• Hospitalize ≥48 h after step-up Doses 1 and 2 for CRS
• CRS signs/symptoms during and for ≥48 h after step-up doses
• CBC with differential; infection prophylaxis (PJP, HSV/VZV antiviral)
• Consider monthly IVIG for recurrent infections / low IgG

Brand names: Elrexfio

Drug class: Monoclonal Antibody

Mechanism of Action

Elranatamab is a humanized IgG2 bispecific antibody that simultaneously engages B-cell maturation antigen (BCMA) expressed on malignant plasma cells and CD3ε on T lymphocytes, redirecting polyclonal cytotoxic T cells to kill BCMA-expressing myeloma cells. Upon dual engagement, T cells form an immunological synapse with the tumor cell, triggering release of perforin and granzymes independent of TCR specificity or MHC-I presentation. The IgG2 backbone reduces Fc-mediated effector functions to minimize off-target immune activation. Continuous target-cell killing proceeds as long as T cells and…

FDA Indications

• Relapsed or refractory multiple myeloma after ≥4 prior lines of therapy including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody (August 2023, accelerated approval; MagnetisMM-3 trial)

Common Side Effects

• CRS (~58%, mostly Grade 1–2)
• Fatigue (~43%)
• Injection site reactions (~40%)
• Neutropenia (~48%)
• Anemia (~46%)
• Thrombocytopenia (~32%)
• Pyrexia (~37%)
• Diarrhea (~28%)
• Nausea (~23%)
• Upper respiratory tract infection (~22%)
• Hypogammaglobulinemia (~22%)
• Hypokalemia (~20%)
• Headache (~18%)

Clinical Pearl

Elranatamab targets BCMA, shared with other approved agents (teclistamab, belantamab mafodotin, CAR-T products); prior anti-BCMA therapy does not necessarily preclude response but may reduce efficacy due to BCMA antigen downregulation. The transition from weekly to Q2W maintenance dosing after 24 weeks is contingent on achieving at least a partial response, making early response assessment critical. Infection prophylaxis (PJP, antiviral for HSV/VZV) should begin at treatment initiation, and…

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