Antibody therapies for multiple myeloma

ABSTRACT

Introduction: Multiple myeloma (MM) is characterized by the uncontrollable proliferation of plasma cells and the excessive production of a specific type of immunoglobulin. Immune system is deregulated in MM and, thus, immunotherapy is a promising therapeutic strategy.

Areas covered: The first approach is to use monoclonal antibodies that recognize specific antigens on the surface of myeloma cells, such as CD38 and B-cell maturation antigen. Upon binding to their target, monoclonal antibodies activate the immune cells to destroy the malignant cell. Anti-CD38 molecules as part of highly effective combination regimens have been approved in both newly diagnosed and relapsed/refractory patients and have significantly changed the myeloma treatment landscape in the recent years. Another strategy is to use antibodies that bind both to a molecule on the surface of the myeloma cell and another molecule on the surface of a T-cell (bispecific antibodies). Consecutively, the T-cell comes close to and recognizes the myeloma cell. These have shown promising results in heavily pre-treated patients.

Expert opinion: Antibody therapy has significantly enhanced the armamentarium against MM. Further research should focus on tailoring the combination regimens based on disease and patient characteristics in order to optimize the efficacy and safety.

KEYWORDS:

• Multiple myeloma
• monoclonal antibody
• bispecific antibody
• CD38
• BCMA
• RANKL

Article highlights

• Immune system is deregulated in myeloma and antibody-based immunotherapy is a promising therapeutic strategy.

• Monoclonal antibodies targeting CD38 and SLAMF7 on the surface of myeloma cells are being introduced in the therapeutic algorithm both in the upfront and in the relapsed setting.

• Monoclonal and bispecific antibodies targeting the B-cell maturation antigen on the surface of myeloma cells have shown significant clinical activity.

• Further research should focus on tailoring the combination regimens based on disease and patient characteristics in order to optimize the efficacy and safety.

Declaration of interest

M Gavriatopoulou declares consultancy and honoraria from Amgen, Karyopharm, Genesis Pharma, Janssen and Takeda. E Terpos declares consultancy and honoraria from BMS, Janssen, Celgene, Takeda, Genesis Pharma, Amgen and Novartis. The authors have no other 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 apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.