The Rationale for Targeting BCMA in Multiple Myeloma

Sagar Lonial MD, FACP: One of the exciting, important developments in the context of myeloma is the realization that BCMA, or B-cell maturation antigen, is an important target in multiple myeloma. We are excited about this target as opposed to others, such as SLAMF7 CD38, because BCMA is much more narrowly expressed on plasma cells. There may be some mature phenotypes of B cells that express BCMA, but their expression numbers are much lower, and it is almost exclusively expressed on mature plasma cells. The target we’re going after is more selective than other targets we have in multiple myeloma.

BCMA is also important for a number of points. A number of things occur to a myeloma cell that has been transformed, including proliferation, drug resistance, and overall survival of myeloma cells, all of which are governed by a BCMA through ligation with its ligands, BAFF and APRIL, which are often circulating in the blood. When BCMA is blocked with a receptor, whether it’s an antibody-drug conjugate, a T-cell engager, or a CAR [chimeric antigen receptor] T cell, you take out 1 of the major resistance factors for malignant plasma cells and potentially may resensitize them to other agents. Additionally, there’s very little expression at all on stem cells and nonhematopoietic cells. The BCMA is in many ways an ideal target in multiple myeloma because of its more selective expression on plasma cells and the role BCMA has in drug resistance.

Transcript Edited for Clarity