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

Kristine A Frerichs, Noemi Anna Nagy, Pieter L Lindenbergh, Patty Bosman, Jhon Marin Soto, Marloes Broekmans, Richard W J Groen, Maria Themeli, Louise Nieuwenhuis, Claudia Stege, Inger S Nijhof, Tuna Mutis, Sonja Zweegman, Henk M Lokhorst, Niels W C J van de Donk

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28 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)197-206
Number of pages10
JournalExpert Review of Clinical Immunology
Issue number3
Publication statusPublished - Mar 2018

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