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

Ahmet Dogan,Alan Fu,Jessica Fowler,Rajesh Belani,Ola Landgren,Nguyet Tran,David Siegel

doi:10.1038/s41408-020-0337-y

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.

Highlights

B-cell maturation antigen (BCMA) plays a critical role in regulating B-cell proliferation and survival, as well as differentiation into plasma cells[1,2]
In this systematic review, BCMA expression was found across multiple hematologic malignancies of precursor Bcells, plasma cells or late-stage B cells (Fig. 2)
In MM, all identified studies reported detectable BCMA expression in all patient samples via protein or mRNA, often at high levels. These results were consistent despite the variability in the number of included patients, laboratory techniques used to assess BCMA levels, and sample types in each study

Summary

Introduction

B-cell maturation antigen (BCMA) plays a critical role in regulating B-cell proliferation and survival, as well as differentiation into plasma cells[1,2]. BCMA is shed from the surface of plasma cells via γ-secretase–mediated cleavage, resulting in a soluble form (sBCMA)[3]. Clinical trials of anti-BCMA therapies, including antibody-drug conjugates, BiTE® (Bispecific T-cell engager) molecules, and chimeric antigen receptor T (CAR T) cell therapy, have demonstrated promising efficacy[5–9]. There is evidence of BCMA expression in other hematologic malignancies, including B-cell leukemias and lymphomas[10,11]. There is currently a lack of systematic reviews integrating knowledge of BCMA expression in hematologic malignancies. The primary objective of this review is to systematically assess the scientific literature and identify which hematologic cancers express BCMA. This review will summarize the evidence for BCMA expression levels in patients with hematologic malignancies

Objectives

Methods

Results

Conclusion