Elotuzumab — Drug Monograph

Brand names: Empliciti

Drug class: Monoclonal Antibody

Mechanism of Action

Elotuzumab is a humanized IgG1 monoclonal antibody that targets Signaling Lymphocytic Activation Molecule Family member 7 (SLAMF7), which is highly expressed on myeloma cells and Natural Killer (NK) cells. It works via a dual mechanism: it directly activates NK cells through both the SLAMF7 pathway and Fc receptors, and it tags myeloma cells for NK cell-mediated destruction through antibody-dependent cellular cytotoxicity (ADCC). Notably, SLAMF7 is not expressed on normal solid tissues or hematopoietic stem cells, providing high specificity for plasma cells.

FDA Indications

• In combination with lenalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received one to three prior therapies.
• In combination with pomalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.

Common Side Effects

• Fatigue
• Diarrhea
• Pyrexia
• Constipation
• Cough
• Peripheral neuropathy
• Nasopharyngitis
• Decreased appetite

Clinical Pearl

Elotuzumab is unique because it has minimal single-agent activity but is highly synergistic with immunomodulatory drugs (iMiDs) like lenalidomide. Clinicians should be aware that Elotuzumab can interfere with serum M-protein monitoring (SPEP) because it is a humanized IgG kappa monoclonal antibody; it may be mistaken for the endogenous M-protein. This is the first monoclonal antibody approved for multiple myeloma that targets an antigen other than CD38.

Related Therapies & Mechanisms

• Daratumumab (Darzalex) — Monoclonal Antibody · Myeloma
• Elranatamab (Elrexfio) — Monoclonal Antibody · Myeloma
• Isatuximab (Sarclisa) — Monoclonal Antibody · Myeloma
• Linvoseltamab (Lynozyfic) — Monoclonal Antibody · Myeloma