Targeting B Cell Maturation Antigen in Patients with Multiple Myeloma: Current Perspectives

Abstract

Relapsed/refractory multiple myeloma remains a challenging disease necessitating the development of more effective treatment options. In the past decade, myeloma therapies have made significant advancements with the introduction of new treatment modalities. One of the new major targets for these novel therapeutics has been B-cell maturation antigen (BCMA), which is expressed on mature B-lymphocytes and plasma cells. There are three main categories of BCMA-targeted therapies currently available, including bispecific antibodies (BsAbs), antibody drug conjugates (ADCs), and chimeric antigen receptor (CAR) T-cell therapies. In this review, we discuss the existing BCMA-targeted therapies and provide insights into currently available treatment and future developments, with a particular focus on clinical efficacy and common drug-related adverse events.

Keywords: B-cell maturation antigen; BCMA; BiTE; CAR T cells; bispecific antibody; multiple myeloma.

Figure 1

Myeloma cell with its receptors and substrates – BAFF and April which are mainly produced by osteoclast, macrophages and bone marrow stromal cells.

Figure 2

ADC binds to BCMA receptor in myeloma cell and gets internalized forming an endosome (yellow dotted circle) releasing toxic payload that leads to myeloma cell death.

Figure 3

Bispecific antibody forms cross linkage with CD3 in T cell and BCMA receptor in myeloma cell that leads to activation of CD4⁺/CD8⁺ T-cell and release of cytotoxic cytokines ultimately causing myeloma cell death.

Figure 4

Signaling domain on CAR T cell binds to BCMA receptor on myeloma cell surface which leads to activation of CAR T cells and release of cytotoxic cytokines leading to myeloma cell lysis and death.