Intro
Aims and Scope
Objective
Preface
Contents
Series Editor Biography
About the Series Editor
Contributors
About the Editors
Chapter 1: The Role of Targeted Therapy in Multiple Myeloma
1.1 Multiple Myeloma Overview
1.2 Historical Treatment of Multiple Myeloma Until Present
1.3 Immunomodulatory Imide Drugs
1.4 Proteasome Inhibitors
1.5 Monoclonal Antibodies
1.6 Histone Deacetylase Inhibitors
1.7 Bone Targeted Therapy
1.8 New Agents on the Horizon
1.9 Conclusion
References
Chapter 2: Lenalidomide
2.1 Introduction

2.2 Indications
2.3 Efficacy of Lenalidomide
2.3.1 Efficacy in Relapsed or Refractory Multiple Myeloma
2.3.1.1 Lenalidomide and Dexamethasone
2.3.1.2 Bortezomib, Lenalidomide, and Dexamethasone
2.3.1.3 Daratumumab, Lenalidomide, and Dexamethasone
2.3.1.4 Carfilzomib, Lenalidomide, and Dexamethasone
2.3.2 Efficacy in Newly Diagnosed Multiple Myeloma
2.3.2.1 Transplant Ineligible Patients
Lenalidomide and Dexamethasone
Cyclophosphamide, Lenalidomide, and Dexamethasone
Bortezomib, Lenalidomide, and Dexamethasone
2.3.2.2 Transplant Eligible Patients

Bortezomib, Lenalidomide, and Dexamethasone
2.4 Mechanisms of Action
2.4.1 Cereblon Pathway
2.4.2 Effect on Cytokines
2.4.3 T Cell Activation
2.4.4 Effect on Natural Killer Cells
2.4.5 Anti-Angiogenic Activity
2.4.6 Direct Antitumor Activity
2.4.7 Myeloma Microenvironment
2.5 Lenalidomide Resistance
2.5.1 Potential Mechanisms of Lenalidomide Resistance
2.5.1.1 Decreased Cereblon Expression and Downstream Factors
2.5.1.2 Increase in c-Myc
2.5.2 Management of Lenalidomide-Resistant Disease
2.5.2.1 Pomalidomide-Based Regimes

2.5.2.2 Proteasome Inhibitor and Daratumumab-Based Regimes
2.6 Conclusion
References
Chapter 3: Pomalidomide
3.1 Introduction
3.2 Clinical Indication of Pomalidomide
3.3 Efficacy
3.3.1 Efficacy in Relapsed and Refractory Multiple Myeloma
3.3.1.1 Pomalidomide and Dexamethasone
3.3.1.2 Pomalidomide + Dexamethasone + Cyclophosphamide
3.3.1.3 Pomalidomide, Bortezomib, and Dexamethasone
3.3.1.4 Pomalidomide, Daratumumab, and Dexamethasone
3.3.1.5 Pembrolizumab, Pomalidomide, and Dexamethasone
3.4 Mechanisms of Pomalidomide Action

3.5 Potential Mechanism of Pomalidomide Resistance and Overcoming Resistance
3.6 Conclusion
References
Chapter 4: Mechanisms Driving Resistance to Proteasome Inhibitors Bortezomib, Carfilzomib, and Ixazomib in Multiple Myeloma
4.1 Introduction
4.2 The Proteasome
4.3 Endoplasmic Reticulum Stress
4.4 Proteasome Inhibitors in Multiple Myeloma
4.5 Bortezomib Resistance Mechanisms
4.5.1 Proteasome Mutation and Overexpression
4.5.2 Drug Efflux
4.5.3 Plasma Cell Differentiation
4.5.4 Upregulation of Heat Shock Proteins
4.5.5 Autophagy