Anti-BCMA antibodies in the future management of multiple myeloma

ABSTRACT

Introduction: B-cell maturation antigen (BCMA) belongs to the tumor necrosis factor receptor family and is expressed on late B-cells and plasma cells. Serum BCMA is elevated in patients with multiple myeloma (MM) and chronic lymphocytic leukemia (CLL), and might represent a novel prognostic and monitoring tool. Serum BCMA levels can predict both progression free survival (PFS) and overall survival (OS). Several therapeutic strategies are currently under investigation including BCMA-directed monoclonal Abs (either naked or with drug conjugates, and bispecific Abs) and cellular T-cell therapies (chimeric antigen receptor T-cells) with impressive clinical results.

Areas covered: This review aims to present the mechanisms of action and the available data on efficacy and safety of therapies targeting BCMA.

Expert opinion: The preliminary preclinical and clinical results from the phase 1 and 2 studies have demonstrated significant activity of the anti-BCMA therapeutic strategies. The main toxicities induced include Cytokine Release Syndrome (CRS) and ocular toxicity. The management of these adverse events remains currently an issue of controversy.

KEYWORDS:

• B-cell maturation antigen
• BiTEs
• CAR-T-cells
• monoclonal antibodies
• multiple myeloma

Article highlights

• BCMA is a surface antigen mainly expressed on late B-cells and plasma cells.

• It might represent a novel blood biomarker to monitor response due to its short half-life

• sBCMA might predict clinical outcomes including PFS and OS

• BCMA is targeted with monoclonal antibodies naked or conjugated, BiTEs and CAR-T-cells

• Several therapeutic strategies are currently under investigation with significant and impressive efficacy results

• The management of the induced toxicity remains an issue of controversy

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A peer reviewer of this manuscript discloses receiving speaker bureau and advisory board honoraria from Celgene, Takeda, and Amgen. The peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.