CD38-targeting antibodies in multiple myeloma: mechanisms of action and clinical experience. (4th March 2018)

• Record Type: Journal Article
• Authors: Frerichs, Kristine A.; Nagy, Noemi Anna; Lindenbergh, Pieter L.; Bosman, Patty; Marin Soto, Jhon; Broekmans, Marloes; Groen, Richard W. J.; Themeli, Maria; Nieuwenhuis, Louise; Stege, Claudia; Nijhof, Inger S.; Mutis, Tuna; Zweegman, Sonja; Lokhorst, Henk M.; van de Donk, Niels W. C. J.
• Is Part Of: Expert review of clinical immunology. Volume 14:Number 3(2018)
• Page Start: 197
• Page End: 206
• Publication Date: 2018-03-04
• Subjects: CD38 antibodies -- multiple myeloma -- smoldering myeloma -- daratumumab -- isatuximab -- MOR202 -- TAK-079 -- immunotherapy; Clinical immunology -- Periodicals; 616.079
• DOI: 10.1080/1744666X.2018.1443809
• Languages: English
• ISSNs: 1744-666X

Abstract

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.