Contents


Preface

Multiple myeloma is a malignant disease characterized by the proliferation of clonal plasma cells in the bone marrow and by the secretion of monoclonal immunoglobulins detected in the serum or urine. Considerable advances have been made in understanding the biology of multiple myeloma through the study of the bone marrow microenvironment. The bone marrow niche appears to play an important role in differentiation, migration, proliferation, survival, and drug resistance of the malignant plasma cells. In multiple myeloma, malignant plasma cells colonize and modify the bone marrow microenvironment through cytokine production and interactions with other cell types. Multiple myeloma cells induce myeloidderived suppressor cells (MDSC) development and survival. MDSCs promote tumor growth and induce immune suppression. Moreover, antimyeloma therapies such as dexamethasone, melphalan, cyclophosphamide, or immunomodulatory drugs can expand and potentiate MDSC immunosuppressive effects. In contrast to these agents, daratumumab depletes MDSCs. Therefore, MDSC suppression could become an important strategy for potentiation of the efficacy of novel immunotherapies (e.g., chimeric antigen receptor T cells or T-cell engager bispecific antibodies). Daratumumab, a CD38 antagonist, functions through different mechanisms of action including an immune-mediated effect (antibody-dependent cytotoxicity; complement-dependent cytotoxicity; antibody-dependent phagocytosis). It can also cause apoptosis through a direct antitumor effect. New findings have helped the development of novel therapeutic drugs for use in combination with cytostatic therapy. Engineering a proper transgenic mouse model for multiple myeloma is very important for understanding biology by defining the relevance of specific genetic lesions in tumorigenesis and the interaction between malignant cells and their surrounding microenvironment. This book discusses all these areas. The introductory chapter deals with selinexor, approved in combination with dexamethasone at earlier relapse. Chapter 2 provides a review of prognostic and predictive factors in newly diagnosed multiple myeloma. Chapter 3 discusses treatment approaches for multiple myeloma. Chapters 4–6 introduce antibody therapies for multiple myeloma and, finally, Chapter 7 analyzes three-dimensional (3D) models mimicking

multiple myeloma bone marrow–microenvironment interactions.

**Ota Fuchs, PhD**

Department of Genomics, Prague, Czech Republic

Institute of Hematology and Blood Transfusion,
