Advances in Biology and Therapy of Multiple Myeloma: Volume 2: Translational and Clinical Research PDF
Preview Advances in Biology and Therapy of Multiple Myeloma: Volume 2: Translational and Clinical Research
Advances in Biology and Therapy of Multiple Myeloma Nikhil C. Munshi • Kenneth C. Anderson Editors Advances in Biology and Therapy of Multiple Myeloma Volume 2: Translational and Clinical Research Editors Nikhil C. Munshi Kenneth C. Anderson Boston VA Healthcare System Department of Medical Oncology and Dana-Farber Cancer Institute Dana-Farber Cancer Institute Harvard Medical School Harvard Medical School Boston, MA, USA Boston , MA, USA ISBN 978-1-4614-5259-1 ISBN 978-1-4614-5260-7 (eBook) DOI 10.1007/978-1-4614-5260-7 Springer New York Heidelberg Dordrecht London Library of Congress Control Number: 2012951132 © Springer Science+Business Media New York 2013 This work is subject to copyright. 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Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a speci fi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) To my parents Gulab and Chandravadan Munshi who have inspired me and taught me what I know and To my wife Medha and sons Vidit and Manit whose love, support, and sacrifi ce helped me become who I am Nikhil C. Munshi To my mentors who sparked my scientifi c and clinical interest in myeloma To my fellow researchers and caregivers, with whom I have been privileged to work To my patients, who are my true heroes and inspire all that I do And to Cynthia, Emily, David, and Peter for their loving support Kenneth C. Anderson Preface Multiple myeloma has evolved from an incurable disease with no therapeutic options fi ve decades ago to a readily treatable disease, based upon increased under- standing of its biology and pathogenesis. Nonetheless, myeloma remains a complex disease driven by both genomic and epigenetic alterations. Moreover, interaction of tumor cells with the bone marrow microenvironment confers additional tumor cell growth, and survival advantage, and drug resistance. Advances in our understand- ing of the pathobiology of the disease have also translated to improved diagnostic and prognostic methods including high-throughput genomics, serum-free light chain, MRI, and PET scanning. Notably, proteasome inhibitors, immunomodula- tory agents, as well as other targeted agents, when used singly or in combination, have transformed myeloma therapy and now achieve unprecedented frequency and extent of response. These rapid advances highlight the need for a state-of-the-art resource focused on the biology of myeloma and its clinical application. Our book describes the basic advances in our understanding of the disease biology and delin- eates molecular mechanisms mediating tumor growth and progression, as well as bone disease and organ dysfunction. Importantly, it provides the preclinical ratio- nale for and clinical ef fi cacy of single and combination targeted therapies directed at the tumor cell in its bone marrow milieu. With an eye toward the future, we update the recent advances using high-density, high-throughput genomic technolo- gies to integrate both DNA and transcriptional changes for improved molecular classi fi cation and personalized therapeutic options. Finally, since studies are already reporting prolonged disease-free survival in myeloma, our book highlights the fact that we are now at the threshold of curative outcome in this disease. Boston , MA , USA Nikhil C. Munshi , M.D. Kenneth C. Anderson , M.D. vii Contents Part I Myeloma Immune and Antibody Targets 1 T Cell Responses in Myeloma ............................................................... 3 Ross Brown, P. Joy Ho, John Gibson, and Douglas Joshua 2 Novel Antigenic Targets for Immunotherapy in Myeloma................. 25 Qing Yi 3 Antibody-Based Therapies in Multiple Myeloma ............................... 43 Yu-Tzu Tai 4 De fi ning Multiple Myeloma as a Target for DNA Vaccines ................ 73 Surinder S. Sahota, Natalia Savelyeva, Debora Joseph-Pietras, Niklas Zojer, and Jason Rice 5 Harnessing Allogeneic Immunity for Anti-myeloma Response ......... 111 Roberto Bellucci and Edwin P. Alyea 6 Dendritic Cells and Peptide-Based Vaccine In Multiple Myeloma ............................................................................. 131 Jooeun Bae, R.H. Prabhala, and Nikhil C. Munshi Part II New Agents 7 Novel Proteasome Inhibitors ................................................................. 157 Robert Z. Orlowski 8 Newer IMiDs ........................................................................................... 181 Abhishek Singla and Shaji Kumar ix
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