An Ex Vivo 3D Co-Culture Model of the Bone Marrow Niche Better Predicts Clinically Relevant Epigenetic Target Modulation to Improve Immunotherapy in Multiple Myeloma

Background

In the last decade, treatment options for multiple myeloma have increased remarkably, including antibodies or CAR-T cells targeting myeloma surface markers with unprecedented efficacy. To enhance immunomodulation and clinical efficacy even more, the combination of these agents with other drugs is highly relevant. A significant association between CD38 expression on myeloma cells and the cytotoxicity of the anti-CD38 antibody daratumumab has been shown. All-trans retinoic acid, the pan-histone deacetylase inhibitor panobinostat, and the enhancer of the zeste homolog 2 inhibitor tazemetostat induce CD38 upregulation and can augment the anti-myeloma effect of daratumumab in conventional cell culture. However, translation into a clinical trial failed.