Multiple Myeloma: Translational and Emerging Therapies PDF

Preface

In the past five years, there has been enormous progress in the translation of basic science to clinical practice in multiple myeloma and other plasma cell dyscrasias. Studies on the genetics and pathogenesis of multiple myeloma and its interaction with the bone marrow microenvironment have paved the way for the development of novel therapeutic agents that have demonstrated exciting activity in vitro and in vivo. These agents moved rapidly from the bench to the bedside and were tested in innovative phase I and II clinical trials, followed by pivotal phase III trials, that changed the management of this disease. In the last four years, the Food and Drug Administration has approved four new agents for multiple myeloma based on the rapid translation of basic science to clinical medicine. Moreover, the rapid leaps in elucidating the biology of myeloma and its interaction with the microenvironment have led to an unprecedented number of novel therapeutic agents being tested for this disease, with over twenty new agents in either preclinical or early clinical trials. Indeed, multiple myeloma has become a model disease for the development of novel therapeutic agents.

In designing the current translational book on multiple myeloma and other plasma cell dyscrasias, including primary systemic amyloidosis and Waldenstro¨ m's macroglobulinemia, we chose to be as inclusive as possible. We wanted a broad representation of genetics, biology, interaction of the malignant cells with their microenvironment, and bone disease in multiple myeloma. We include current treatment options for patients with relapsed or refractory disease, for newly diagnosed, untreated patients, and in clinical trials in early development. We also include advances in translational research in two closely related plasma cell dyscrasias-primary systemic amyloidosis and Waldenstro¨ m's macroglobulinemia.

The first three chapters discuss the molecular biology, genetics, and cytogenetics of multiple myeloma, as well as molecular mechanisms of growth and resistance of the malignant cells, and current animal models. We have included a chapter on the role of the bone marrow microenvironment in multiple myeloma, including myeloma bone disease and the homing and migration of multiple myeloma cells. The next chapter defines novel therapeutic agents being tested in the preclinical setting and moving forward into clinical practice. This represents the interface between basic science and clinical research. The fourth chapter begins with the clinical long-term followup of monoclonal gammopathy and its progression to multiple myeloma. It is followed by an up-to-date assessment of the prognostic factors and classifications of multiple myeloma, which leads to chapters updating therapy for patients with multiple myeloma. These include novel options for therapy in newly diagnosed patients and in patients with relapsed or refractory disease, as well as promising new agents in early phase I and II clinical trials, and immunotherapies in multiple myeloma. Finally, we discuss advances in the biology and therapy of patients with primary systemic amyloidosis and Waldenstro¨ m's macroglobulinemia.

This book is the first in its category to address the rapid advances in translational research in multiple myeloma and other plasma cell dyscrasias. Its production has required the cooperation of our many contributors. We are grateful to them for providing us with up-to-date chapters that have made this comprehensive work possible. We also appreciate the hard work of our publisher, who helped with the coordination, revisions, and structure of our text. We look forward to further advances in the biology of multiple myeloma and its interaction with the microenvironment, as the rapid translation of basic research to innovative clinical trials will prolong survival and improve the quality-of-life of our patients with multiple myeloma and other plasma cell dyscrasias.