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.

Fig. 1. Identification of relevant publications.

a Animal studies, studies using non-human and/or non-hematologic cell lines, studies investigating non-hematologic conditions, review articles, comments, editorials, letters, guidelines, legal cases, debates, newspaper articles, opinions, protocols, workshops, patient education brochures, and non-English publications were excluded. b Three studies were identified from reference lists of review publications.

Fig. 2. BCMA expression in normal B-cell development and in hematologic malignancies.

In the top part of the figure, normal B-cell development is shown from left to right starting from pro-B-cell to the terminally differentiated plasma cell. The presence of immunoglobulin and BCMA expression is indicated in each developmental stage. In the bottom half of the figure, the cell of origin of various mature B-cell malignancies and relative intensity of BCMA expression are shown.