CD38-targeting antibodies in multiple myeloma: mechanisms of action and clinical experience

ABSTRACT

Introduction: Multiple myeloma (MM) is generally an incurable hematological malignancy with heterogeneous overall survival rates ranging from a few months to more than 10 years. Survival is especially poor for patients who developed disease that is refractory to immunomodulatory drugs and proteasome inhibitors.

Areas covered: This review will discuss the importance of CD38-targeting antibodies for the treatment of MM patients to improve their outcome.

Expert commentary: Intense immuno-oncological laboratory research has resulted in the development of functionally active monoclonal antibodies against cell surface markers present on MM cells. In this respect, CD38-targeting antibodies such as daratumumab, MOR202, and isatuximab, have high single agent activity in heavily pretreated MM patients by virtue of their pleiotropic mechanisms of action including Fc-dependent effector mechanisms and immunomodulatory activities. Importantly, CD38-targeting antibodies are well tolerated, with infusion reactions as most frequent adverse event. Altogether, this makes them attractive combination partners with other anti-MM agents. Daratumumab is already approved as monotherapy and in combination with lenalidomide-dexamethasone as well as bortezomib-dexamethasone in pretreated MM patients. Furthermore, results from studies evaluating CD38-targeting antibodies in newly diagnosed MM patients are also promising, indicating that CD38-targeting antibodies will be broadly used in MM, resulting in further improvements in survival.

KEYWORDS:

• CD38 antibodies
• multiple myeloma
• smoldering myeloma
• daratumumab
• isatuximab
• MOR202
• TAK-079
• immunotherapy

Declaration of interest

NWCJ van de Donk serves in advisory boards for Janssen Pharmaceuticals, Celgene, AMGEN, BMS, Novartis, Bayer and Servier; and received research support from Janssen Pharmaceuticals, Celgene, Amgen, and BMS. R Groen, T Mutis and H Lokhorst have received research support from Janssen Pharmaceuticals. S Zweegman has received research funding from Celgene, Janssen, and Takeda; and serves in advisory boards for Celgene, Janssen, Takeda, AMGEN, and Sanofi. 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.

Additional information

Funding

This article was not funded.