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.
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.