Bispecific antibodies for multiple myeloma: past, present and future

Despite the development of various therapeutic agents, multiple myeloma remains incurable. Recently, T-cell redirected immunotherapy has become a promising strategy for the treatment of refractory myeloma. Clinical trials using chimeric antigen receptor (CAR)-T cells and bispecific antibodies have demonstrated successful anti-myeloma responses in triple-class-refractory patients. However, unique and unwanted immune effects associated with on-target/off-target reactivity of activated immune cells need to be considered and properly managed. This review summarizes recent advances in bispecific antibodies for the treatment of refractory myeloma. It outlines the history of their development, along with a discussion of their mechanisms of action and their current and potential future role in myeloma therapy. As more evidence emerges to inform the timing of CAR-T-cell therapy, the results of clinical trials and off-the-shelf nature of bispecifics also suggest the timing of their treatment. These findings will promote further development and application of bispecifics for refractory myeloma in combination with other appropriate agents.