Current status and future prospects of immunotherapy for multiple myeloma

Abstract

The introduction of autologous stem cell transplantation, proteasome inhibitors, and immunomodulatory drugs (IMiDs) has improved the treatment outcome for multiple myeloma (MM). However, many patients develop resistance to existing therapies, and novel treatment strategies for these patients must be established. Therapeutic antibodies including daratumumab targeting CD38 and elotuzumab targeting SLAMF7 have been introduced in the clinic as immunotherapies for MM. These antibodies exert cytotoxic effects on myeloma cells through the activation of effector cells such as natural killer cells and induction of phagocytosis by macrophages. Suppressed anti-tumor immunity may be related to acquisition of drug resistance by myeloma cells in patients with MM. It has been reported that IMiDs such as lenalidomide and pomalidomide enhance the effect of therapeutic antibodies through the stimulation of anti-tumor immunity. This stimulation of anti-tumor immunity is also observed in the effects of anti-CD38 antibodies, such as daratumumab and isatuximab. Therefore, it is expected that combination therapy with anti-CD38 antibodies and IMiDs may enhance anti-tumor immunity. Furthermore, chimeric antigen receptor (CAR) T cell therapy, antibody drug conjugates (ADC), and bispecific antibodies (BsAbs) are in the process of their introduction to the clinic as novel immunotherapies for MM.