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Multiple Myeloma: Biologic Understanding and Curative Outcome — Pushing the Envelope
Foreword Multiple Myeloma: Biologic Understanding and Curative Outcome – Pushing the Envelope Clinical Lymphoma & Myeloma, Vol. 9, Suppl. 2, S2, 2009; DOI: 10.3816/CLM.2009.s.008 In the past 25 years, since the first International Myeloma Workshop in Oxford, England, there has been a phenomenal advance in our understanding of the biology of multiple myeloma (MM) and its available therapeutic options. Myeloma has become a disease that has defined translational medicine, and its management has changed from palliative approaches to that of a disease with curative potential. In the past 5 years, 5 new FDA/ EMEA approvals for 4 new drugs—thalidomide (T), bortezomib (V), lenalidomide (R), and pegylated liposomal doxorubicin— have been obtained, and there are 3 large phase III studies under way that might provide access to additional new therapeutic agents in this disease. The XII International Myeloma Workshop in Washington, DC, represents an important landmark in the growth of our understanding of this disease. As the abstract and educational books for this meeting demonstrate, a new era has been ushered in with focus on developing individualized medicine, detection of genomic lesions using the high-throughput technologies, development of targeted agents focused on overcoming genetic lesions, and clinical studies not only focused on improving the outcome but also quality of life. The advances in diagnostic methods include incorporation of serum free light chain to evaluate the disease activity, to predict progression in early-stage plasma cell disorders, and to more stringently define complete response (CR). Besides the diagnostic importance, magnetic resonance imaging, multicolor immunofluorescence analysis of malignant plasma cells from bone marrow, and molecular techniques are providing new avenues that might eventually help to detect minimal residual disease and help predict curative outcome. The use of high-throughput genomics and proteomics in myeloma will help develop improved prognostic models and eventually formulate individualized therapy. The results being discussed at this workshop attests to this advance. The high-density high-throughput array technology now provides a global view of the genomic changes in MM at both DNA and transcriptional levels as well as post-translational and transcriptional modifications. This technological advance now allows us to molecularly reclassify myeloma and provide the scientific rationale for novel targeted therapies. Driven by this information, in 2008, 13 new agents were undergoing clinical evaluation in myeloma.
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Similarly, a revolutionary change has occurred in therapeutic modalities in MM. At the time of first workshop almost 25 years ago, the first patient was treated with VAD regimen and the first patient was yet to receive autologous bone marrow transplantation for myeloma. Since the 1990s, high-dose chemotherapy supported by autologous peripheral blood stem cell transplantation has become the standard of care in younger patients, achieving higher complete responses and improved survival. In this meeting, we will be discussing 3 new novel agent combinations achieving 95%100% overall responses—including 20%-30% CRs—without using high-dose therapy. There has been a doubling of life expectancy for all patients, young and old. Thus, MM is changing from an enigmatic disease with few effective systemic therapies to a disease with unraveled molecular and signaling events and an enhanced treatment armamentarium. With the main goal of stimulating debate and discussion, this meeting features scientific presentations from leading myeloma researchers worldwide, covering all aspects of the disease, from fundamental basic concepts to current clinical trials. Importantly, this workshop will present 3 consensus panel reports on some of the most pressing issues that demand uniformity and cohesiveness. The workshop features a special section in which leaders of various cooperative groups from around the world will not only update us on recently completed trials but also give us an overview of ongoing and planned trials so that participants and researchers can grasp the specific questions being addressed worldwide and develop intergroup efforts. Finally, this workshop will inaugurate the formation of the International Myeloma Society. The aims of the society are to promote research, education, clinical studies (including diagnosis and treatment), workshops, and symposia on all aspects of multiple myeloma and related disorders worldwide. We would like to thank all the participants in the XII International Myeloma Workshop. We hope that you will enjoy the meeting and your visit to Washington, DC.
Nikhil C. Munshi, MD S. Vincent Rajkumar, MD Vinod Raina, MD Sundar Jagannath, MD
Clinical Lymphoma & Myeloma Supplement February 2009
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Similarly, a revolutionary change has occurred in therapeutic modalities in MM. At the time of first workshop almost 25 years ago, the first patient was treated with VAD regimen and the first patient was yet to receive autologous bone marrow transplantation for myeloma. Since the 1990s, high-dose chemotherapy supported by autologous peripheral blood stem cell transplantation has become the standard of care in younger patients, achieving higher complete responses and improved survival. In this meeting, we will be discussing 3 new novel agent combinations achieving 95%100% overall responses—including 20%-30% CRs—without using high-dose therapy. There has been a doubling of life expectancy for all patients, young and old. Thus, MM is changing from an enigmatic disease with few effective systemic therapies to a disease with unraveled molecular and signaling events and an enhanced treatment armamentarium. With the main goal of stimulating debate and discussion, this meeting features scientific presentations from leading myeloma researchers worldwide, covering all aspects of the disease, from fundamental basic concepts to current clinical trials. Importantly, this workshop will present 3 consensus panel reports on some of the most pressing issues that demand uniformity and cohesiveness. The workshop features a special section in which leaders of various cooperative groups from around the world will not only update us on recently completed trials but also give us an overview of ongoing and planned trials so that participants and researchers can grasp the specific questions being addressed worldwide and develop intergroup efforts. Finally, this workshop will inaugurate the formation of the International Myeloma Society. The aims of the society are to promote research, education, clinical studies (including diagnosis and treatment), workshops, and symposia on all aspects of multiple myeloma and related disorders worldwide. We would like to thank all the participants in the XII International Myeloma Workshop. We hope that you will enjoy the meeting and your visit to Washington, DC.
Nikhil C. Munshi, MD S. Vincent Rajkumar, MD Vinod Raina, MD Sundar Jagannath, MD
Clinical Lymphoma & Myeloma Supplement February 2009