B-cell maturation antigen expression across hematologic cancers: a systematic literature review

Abstract

B-cell maturation antigen (BCMA) plays a critical role in regulating B-cell proliferation and survival. There is evidence for BCMA expression in various hematologic malignancies, suggesting that BCMA may play an important role as a biomarker or therapeutic target in these diseases. Given advances in understanding the role of BCMA in B-cell development and the promise of BCMA as a therapeutic target, a systematic review is needed to rigorously assess the evidence for BCMA expression and identify areas of consensus and future research. The objective of this review was to summarize the evidence on BCMA protein and mRNA expression across hematologic malignancies. Using a PubMed database search up to 28 August 2019, a systematic literature review of publications reporting BCMA expression in patients with hematologic malignancies was conducted. Data from published congress abstracts presented at the American Society of Clinical Oncology and the American Society of Hematology were also searched. Studies that assessed BCMA expression (protein or mRNA) in patients of any age with hematologic malignancies were included. A total of 21 studies met inclusion criteria and were included in the review. BCMA was expressed in several hematologic malignancies, including multiple myeloma (MM), chronic lymphocytic leukemia, acute B-lymphoblastic leukemia, non-Hodgkin lymphoma (NHL), and Hodgkin lymphoma. BCMA was expressed at uniformly high levels across all 13 MM studies and at low to moderate levels in acute myeloid leukemia and acute lymphoblastic leukemia. These results suggest that BCMA is a relevant target in MM as well as in a subset of B-cell leukemia. BCMA expression in Hodgkin lymphoma and NHL varied across studies, and further research is needed to determine the utility of BCMA as an antibody target and biomarker in these diseases. Differences in sample type, timing of sample collection, and laboratory technique used may have affected the reporting of BCMA levels.

Mechanisms of Action of the New Antibodies in Use in Multiple Myeloma

“…BCMA (also referred as TNFRSF17, CD269) is a transmembrane glycoprotein belonging to the tumor necrosis factor superfamily, selectively induced during B-cell differentiation into plasmablasts and bone marrow PCs ( 121 ), neoplastic PCs ( 120 , 122 ), while it is nearly absent on naive and memory B cells ( 121 , 122 ) CD34 stem cells, and other normal tissue cells ( 123 ) ( Table 1 ). In normal and neoplastic mouse plasma cells, and in the human MM cell line MM1.s, the BCMA expression is under control of the master plasma cell gene IRF4 ( 124 , 125 ), even if the post-translational regulation of BCMA can be largely compensated for reduced transcription, by mechanisms still under investigation ( 124 ).…”

“…Talquetamab (JNJ-64407564) is a GPRC5D x CD3 DuoBody able, in vitro , to induce cytotoxicity independently from the number of BCMA receptors or the amount of sBCMA, and, in vivo , to recruit T cells at the tumor site, without affecting humoral immunity due to lack of expression on B memory cells. Robust preclinical data provided the rationale for the ongoing phase NCT03399799I clinical trial ( 122 ).…”

Antibody‐Drug‐Conjugate Therapy for Hematological Cancers: Matching Cell Biology with Clinical Benefit

“…Belantamab recognizes the B-cell maturation antigen (BCMA, CD269), a transmembrane glycoprotein [109] expressed at high levels during plasma cell differentiation of plasmablasts and on mature plasmacytes, but only sparingly on antigen-naïve and memory B cells [110,111] and not on normal non-immunological tissues. [111] It is almost ubiquitously expressed on MM cells [112] and expression levels correlate with disease progression. [113] Furthermore, the binding of BCMA to ligands B cell activating factor (BAFF) and proliferation-inducing ligand (APRIL) leads to activation of nuclear factor kappa-B pathways and the transcription of genes required for the survival of long-lived plasma cells.…”

Flow cytometric myeloma measurable residual disease testing in the era of targeted therapies

“…Several solutions have been proposed to the problem of loss of CD38 expression or detection in daratumumab‐treated patients. Novel plasma cell markers such as CD54 (ICAM‐1), 41 CD229 (SLAMF3), 41 CD269 (BCMA), 42 and CD319 (SLAMF7) 41 have been proposed with limited adoption, specificity, and performance (based on personal experience and correspondences among clinical flow cytometry laboratories). Unfortunately, these markers have themselves become targets of therapy 42‐44 which will likely limit their clinical utility in the long term.…”