BCMA in Multiple Myeloma—A Promising Key to Therapy

Abstract

Despite the discoveries of numerous agents including next generation proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, multiple myeloma (MM) remains an incurable disease. The field of myeloma treatment in refractory or relapsed patients after standard therapy entered a new era due to the B-cell maturation antigen (BMCA) targeted approach. BCMA is a member of the tumor necrosis factor receptor family with high expression in mature B-lymphocytes and plasma cells. Given the understanding of BCMA mechanism of action in MM, BCMA plays a promising role as a therapeutic target. Several clinical trials are underway to evolve the current BCMA targeted treatment concept such as antibody-drug conjugates (ADCs), bispecific T cell engagers (BITEs) and chimeric antigen receptor (CAR) T cell therapy. Current results of representative BCMA trials may close the gap of the unmet clinical need to further improve the outcome of heavily pretreated MM patients with the potency to change the paradigm in newly diagnosed and refractory MM. This comprehensive review will give an update on various BMCA targeted treatment modalities (ADCs, BITEs, CAR T cell therapy) and its existing results on efficacy and safety from preclinical and clinical trials.

Second Booster BNT162b2 Restores SARS-CoV-2 Humoral Response in Patients With Multiple Myeloma, Excluding Those Under Anti-BCMA Therapy

“…This finding may indicate a cumulative effect of BCMA-targeting therapies in the sustained depletion of B-cells, which in turn results in defective antibody production. 25 , 26 …”

Targeting BCMA to Treat Multiple Myeloma: Updates From the 2021 ASH Annual Meeting

“…For instance, anti-BCMA CAR-T-cell therapy with better performance requires more complex preparation conditions and more expensive treatment costs, which are difficult for ordinary families to afford ( 130 ). For BsAbs, because of the relatively short half-life period ( 131 ), they need to extend the infusion time or improve the medication frequency to maintain its efficacy ( 132 ), which also increases the costs of treatment. BiTE depends on the quality of T cells, thus it is mainly used for front-line treatment ( 133 , 134 ).…”

Pathways of Angiogenic and Inflammatory Cytokines in Multiple Myeloma: Role in Plasma Cell Clonal Expansion and Drug Resistance

“…Recent investigations have also shown that BCMA may represent a biomarker for the diagnosis of, monitoring of and therapeutic response to MM treatments, in both MM patients with secretory features (i.e., presence of tumour-related factors in peripheral blood) and in patients with non-secretory MM, in which it is more difficult to track the disease using conventional markers. Therefore, circulating BCMA may be helpful in detecting MM and also drug resistance [ 132 ].…”