Multiple Myeloma - A New Era of Treatment Strategies


by

Klaus Podar, Kenneth C. Anderson

DOI: 10.2174/97816080529741120101
eISBN: 978-1-60805-297-4, 2012
ISBN: 978-1-60805-609-5



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Indexed in: Book Citation Index, Science (BKCI-S), Web of Science, Scopus

Multiple Myeloma (MM), the second most common blood cancer in adults, is a clonal plasma cell malignancy within the bone marrow charac...[view complete introduction]

Table of Contents

Foreword

- Pp. i

S. Vincent Rajkumar

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Preface

- Pp. ii-iii (2)

Klaus Podar and Kenneth C. Anderson

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List of Contributors

- Pp. iv-vi (3)

Klaus Podar and Kenneth C. Anderson

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A Short History of Multiple Myeloma

- Pp. 3-14 (12)

Robert A. Kyle and David P. Steensma

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Epidemiology and Etiology of Multiple Myeloma

- Pp. 15-57 (43)

Brenda M. Birmann, Brian C.-H. Chiu, Kristin Muench, Catherine A. Suppan and Wendy Cozen

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Genetic and Epigenetic Mechanisms in Multiple Myeloma

- Pp. 58-72 (15)

Michela Frenquelli and Giovanni Tonon

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Guideline to Multiple Myeloma Treatment Strategies

- Pp. 73-87 (15)

Klaus Podar, Jonathan L. Kaufmann, Jacob P. Laubach, Sagar Lonial, Paul G. Richardson and Kenneth C. Anderson

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The Role of Stem Cell Transplantation in Multiple Myeloma

- Pp. 88-96 (9)

Jean-Luc Harousseau

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Pathogenesis and Treatment of Bone Disease in Multiple Myeloma

- Pp. 97-106 (10)

Sonia Vallet and Noopur Raje

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Management of Complications in Multiple Myeloma

- Pp. 107-119 (13)

Suzanne Lentzsch

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Promising Clinical Trials in Multiple Myeloma

- Pp. 120-127 (8)

Shaji Kumar

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The Multiple Myeloma Bone Marrow Microenvironment

- Pp. 128-137 (10)

Aldo M. Roccaro, Angelo Vacca, Giuseppe Rossi and Irene Ghobrial

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Multiple Myeloma Bone Marrow Angiogenesis

- Pp. 138-148 (11)

Domenico Ribatti and Angelo Vacca

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Mouse Models of Multiple Myeloma: Advantages and Pitfalls

- Pp. 149-160 (12)

Mariateresa Fulciniti, Paola Neri, Pierosandro Tagliaferri and Pierfrancesco Tassone

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New Therapeutic Strategies in Multiple Myeloma

- Pp. 161-183 (23)

Klaus Podar, Teru Hideshima, Dharminder Chauhan and Kenneth C. Anderson

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Antibody-based Therapies in Multiple Myeloma

- Pp. 184-199 (16)

Yu-Tzu Tai

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Index

- Pp. 200-204 (5)

Klaus Podar and Kenneth C. Anderson

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Foreword

The pace at which myeloma therapy has evolved in recent years has been nothing short of spectacular. Conventional textbooks can scarcely keep up with the advances. This electronic book edited by Dr. Klaus Podar and Kenneth Anderson is therefore both timely and appropriate. I would like to congratulate the editors for assembling a stellar cast of investigators to author the various chapters in this e-Book. The editors and authors have done a masterful job with the content and organization of the e-Book. I am sure this e Book will be an invaluable resource for physicians worldwide.

S. Vincent Rajkumar,
Mayo Clinic
USA


Preface

Multiple Myeloma (MM), the second most common blood cancer in adults, is a clonal plasma cell malignancy within the bone marrow characterized by osteolytic bone lesions, renal disease, and immunodeficiency. The development of MM is a complex multi-step process involving both early and late genetic changes in the tumor cell as well as selective supportive conditions by the bone marrow (BM) microenvironment. It is now well established that MM cell-induced disruption of the bone marrow homeostasis between the highly organized cellular and extracellular compartments supports MM cell proliferation, survival, migration, and drug resistance via activation of various signaling (e.g. PI3K/Akt, JAK/ Stat-, Raf/MEK/MAPK-, NFκB-, and Wnt-) pathways. Based on this knowledge prototypic drugs thalidomide, bortezomib, and lenalidomide, which target both MM cells and the BM microenvironment have already fundamentally changed treatment options of this disease. Indeed, their benefit is now not only shown in relapsed and refractory disease but they also improve overall response, duration of response, and progression-free and overall survival when used as part of first-line regimens. However, despite these new insights into MM pathogenesis and exciting derived therapeutic advances, MM still remains incurable. Ongoing studies are therefore aiming to further delineate mechanisms of MM pathogenesis within the bone marrow to identify novel agents with enhanced cytotoxicity and decreased drug resistance to improve patient outcome.

We are very happy having been able to win eminent physician/ scientists to write the chapters of this e-Book which aims to provide readers with a comprehensive account of the most recent developments in the field of MM; a field which we believe represents a paradigm for translational research in general. Our foremost goal was to address a broad audience of readers including clinicians, scientists, students, and interested patients.

After a brief historic review by Drs. Kyle and Steensma, Section 1 will cover newest insights into the epidemiology and etiology of MM (Drs. Birmann and colleagues), as well as attempts to generate a genetically based classification system (Dr. Tonon).

In Section 2, Dr. Podar and colleagues will first give a brief overview of up-to-date treatment strategies both for upfront therapy as well as for therapy of relapsed/ refractory MM. Dr. Harousseau will then specifically focus on the changing role of autologous and allogeneic stem cell transplantation as part of new treatment regimens. Drs Vallet and Raje will review the pathophysiology and treatment options of MM bone disease thereby identifying potential therapeutic alternatives to bisphosphonates. Dr. Lentzsch will then discuss the management of complications in MM and supportive treatment regimens. Finally, Dr. Kumar will summarize promising advanced clinical trials, which are likely to change once more MM treatment regimens in near future. Taken together, Section 2 aims to address the needs of clinicians who are looking for the rationale of up-to-date treatment guidelines in the day-to-day practice.

In Section 3 exciting new preclinical results will be discussed. Chapters of this section will delineate the pathophysiologic key role of the BM microenvironment in MM (Dr. Roccaro and colleagues), and the role of MM BM angiogenesis (Drs. Ribatti and Vacca), in particular. Moreover, Drs. Fulciniti and colleagues will discuss MM mouse models, their advantages and pitfalls in translational MM research.

Based on mechanistic data presented in Section 3, Section 4 will finally summarize potential new therapeutic targets and derived new treatment strategies with focus on small molecules (Drs. Podar and colleagues), as well as antibodies (Dr. Tai).

Sections 3 and 4 aim to predominantly address the interests of scientists and clinical investigators in the MM field. However, we hope and believe that our own and other studies of the pathophysiologic role of the tumor microenvironment, the identification of novel therapeutic targets, and the clinical introduction of derived agents in MM also may serve as a paradigm for translational research in other fields of oncology.

Klaus Podar
National Center of Tumor Diseases (NCT), University of Heidelberg and
German Cancer Research Center (DKFZ), Germany;
Dana-Farber Cancer Institute (DFCI),
Harvard Medical School, USA

Kenneth C. Anderson
Dana-Farber Cancer Institute (DFCI),
Harvard Medical School,
USA

List of Contributors

Editor(s):
Klaus Podar
Dana-Farber Cancer Institute (DFCI)
Harvard Medical School
USA


Kenneth C. Anderson
Dana-Farber Cancer Institute (DFCI)
Harvard Medical School
USA




Contributor(s):
Kenneth C. Anderson
Kraft Family Professor of Medicine
Medical Director, Kraft Family Blood Center
The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center
Department of Medical Oncology
Dana Farber Cancer Institute
Harvard Medical School
Boston
MA
USA


Brenda M. Birmann
Instructor in Medicine/ Harvard Medical School
Channing Laboratory
Department of Medicine
Brigham and Women's Hospital and Harvard Medical School
Boston
MA
USA


Dharminder Chauhan
Principal Associate in Medicine
The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center
Department of Medical Oncology
Dana Farber Cancer Institute
Harvard Medical School
Boston
MA
USA


Brian C.-H. Chiu
Associate Professor of Epidemiology, Department of Health Studies
University of Chicago
USA


Wendy Cozen
Associate Professor of Preventive Medicine and Pathology
Department of Preventive Medicine and Pathology
Norris Comprehensive Cancer Center
Keck School of Medicine
University of Southern California
Los Angeles
CA
USA


Michela Frenquelli
Postdoctoral Fellow
Division of Molecular Oncology
San Raffaele del Monte Tabor Scientific Foundation
Milan
Italy


Mariateresa Fulciniti
Postdoctoral Fellow
The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center
Department of Medical Oncology
Dana Farber Cancer Institute
Harvard Medical School
Boston
MA
USA


Irene Ghobrial
Assistant Professor of Medicine, Department of Medicine
Harvard Medical School
Kirsch Lab for Waldenstrom Macroglobulinemia
Department of Medical Oncology
Dana Farber Cancer Institute
Harvard Medical School
Boston
MA
USA


Jean-Luc Harousseau
Professor of Medicine
René Gauducheau Cancer Center
Nantes/ St Herblain
France


Teru Hideshima
Principal Associate in Medicine
The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center
Department of Medical Oncology
Dana Farber Cancer Institute
Harvard Medical School
Boston
MA
USA


Jonathan L. Kaufman
Assistant Professor of Medicine
Department of Hematology and Medical Oncology Winship Cancer Institute
Emory University School of Medicine
Atlanta
GA
USA


Shaji Kumar
Associate Professor of Medicine, Department of Medicine
Division of Hematology
Mayo Clinic
Rochester
MN
USA


Robert A. Kyle
Professor of Medicine, Department of Medicine
Division of Hematology
Mayo Clinic
Rochester
MN
USA


Jacob P. Laubach
Instructor in Medicine, Department of Medicine
Harvard Medical School
The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center
Department of Medical Oncology
Dana Farber Cancer Institute
Harvard Medical School
Boston
MA
USA


Suzanne Lentzsch
Assistant Professor of Medicine
Division of Hematology/Oncology
University of Pittsburgh Cancer Institute
Pittsburgh
PA
USA


Sagar Lonial
Associate Professor of Medicine, Vice Chair of Clinical Affairs
Department of Hematology and Medical Oncology Winship Cancer Institute
Emory University School of Medicine
Atlanta
GA
USA


Kristin Muench
Research Associate, Department of Preventive Medicine
Norris Comprehensive Cancer Center
Keck School of Medicine
University of Southern California
USA


Paola Neri
Postdoctoral Fellow
Division of Hematology and Bone Marrow Transplant
University of Calgary
AB
Canada


Klaus Podar
Associate Professor of Medicine
Principal Investigator and Group Leader at the National Center for Tumor Diseases (NCT)
University of Heidelberg and German Cancer Research Center (DKFZ)
Germany
/
Visiting Professor at The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center
Department of Medical Oncology
Dana Farber Cancer Institute
Harvard Medical School
Boston
MA
USA


Noopur Raje
Associate Professor of Medicine
Division of Hematology-Oncology
Massachusetts General Hospital Cancer Center
Harvard Medical School
Boston
MA
USA


Paul G. Richardson
Associate Professor of Medicine
The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center
Department of Medical Oncology
Dana Farber Cancer Institute
Harvard Medical School
Boston
MA
USA


Aldo Roccaro
Research Scientist/Research Associate in Medicine
Harvard Medical School
Dana-Farber Cancer Institute
Boston
MA
USA


Giuseppe Rossi
Director of Hematology
Spedali Civili di Brescia
Brescia
Italy


Domenico Ribatti
Professor of Medicine
Department of Human Anatomy and Histology
Bari
Italy


David P. Steensma
Lecturer on Medicine, Department of Medicine
Harvard Medical School
Oncology, Brigham And Women's Hospital
Boston
MA
USA


Catherine A. Suppan
Research Assistant
Channing Laboratory
Department of Medicine
Brigham and Women's Hospital
Boston
MA
USA


Pierosandro Tagliaferri
Professor of Medicine
Medical Oncology Unit
University of Magna Græcia and T. Campanella Cancer Center
Catanzaro
Italy


Pierfrancesco Tassone
Professor of Medicine
Medical Oncology Unit
University of Magna Græcia and T. Campanella Cancer Center
Catanzaro
Italy


Giovanni Tonon
Head, Functional Genomics of Cancer Unit
Division of Molecular Oncology
Scientific Coordinator
Multiple Myeloma Unit
Department of Oncology
San Raffaele del Monte Tabor Scientific Foundation
Milan
Italy


Angelo Vacca
Professor of Medicine
Department of Internal Medicine and Clinical Oncology
Bari
Italy


Sonia Vallet
Postdoctoral Fellow
Division of Hematology-Oncology
Massachusetts General Hospital Cancer Center
Harvard Medical School
Boston
MA
USA




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