Advances in Biology and Therapy of Multiple Myeloma: Volume 2: Translational and Clinical Research

291 Pages·2013·2.424 MB·English

by  Ross Brown, P. Joy Ho, John Gibson, Douglas Joshua (auth.), Nikhil C. Munshi, Kenneth C. Anderson (eds.)

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
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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