Therapeutic antibodies for multiple myeloma

In recent years, many antibody therapies for multiple myeloma have been developed. Antibodies against SLAMF7, CD38, B-cell maturation antigen and PD-1 have been developed and clinical trials are currently under way. As of July 2017, antibodies clinically available in Japan for the treatment of multiple myeloma are elotuzumab against SLAMF7 and daratumumab against CD38. Elotuzumab is a humanized IgG1-kappa monoclonal antibody targeting human SLAMF7. SLAMF7 is a cell surface glycoprotein receptor highly expressed on multiple myeloma cells, and it is also expressed on natural killer cells and is critical for natural killer function. Binding of elotuzumab to natural killer cells leads to activation of natural killer cells, resulting in antibody-dependent cell-mediated cytotoxicity of elotuzumab-bound multiple myeloma cells, but not complement-dependent cytotoxicity. The result of a randomized phase III trial of elotuzumab+lenalidomide+dexamethasone (ELOQUENT-2) reduced the risk of disease progression/death by 30% vs lenalidomide+dexamethasone in relapse/refractory multiple myeloma. Daratumumab is a human anti-CD38 IgG1-kappa antibody. CD38 is expressed ubiquitously virtually in all tissues that are highly expressed on plasma cells and it represents an attractive target for immunotherapy using monoclonal antibodies. In the phase III CASTOR trial, patients treated with daratumumab+bortezomib+dexamethasone had a better CR rate and progression-free survival rate compared with bortezomib+dexamethasone-treated patients (29% vs 10%, median progression-free survival: 16.7 vs 7.1 months, respectively). Moreover, in the phase III POLLUX trial, patients treated with daratumumab+lenalidomide+dexamethasone had a better response and progression-free survival (CRR or better: 55% vs 23%, 30-month progression-free survival: 58% vs 35%), compared with lenalidomide+dexamethasone-treated patients.