Multiple myeloma (MM) is a plasma cell
malignancy and the second most common
hematological neoplasm in adults, comprising 1.8% of all
cancers. With an annual incidence of ~30,770 cases in the United States, MM has a high mortality rate, leading to 12,770 deaths per year. MM is a genetically complex, highly heterogeneous
malignancy, with significant inter- and intra-patient clonal variability. Recent years have witnessed dramatic improvements in the diagnostics, classification, and treatment of MM. However, patients with high-risk disease have not yet benefited from therapeutic advances. High-risk patients are often primary refractory to treatment or relapse early, ultimately resulting in progression toward aggressive end-stage MM, with associated extramedullary disease or
plasma cell leukemia. Therefore, novel treatment modalities are needed to improve the outcomes of these patients.
Bispecific antibodies (BsAbs) are immunotherapeutics that simultaneously target and thereby redirect effector immune cells to
tumor cells. BsAbs have shown high efficacy in B cell
malignancies, including refractory/relapsed
acute lymphoblastic leukemia. Various BsAbs targeting MM-specific
antigens such as
B cell maturation antigen (
BCMA), CD38, and CD138 are currently in pre-clinical and clinical development, with promising results. In this review, we outline these advances, focusing on BsAb drugs, their targets, and their potential to improve survival, especially for high-risk MM patients. In combination with current treatment strategies, BsAbs may pave the way toward a cure for MM.