New Genetic Insights and Therapy in Multiple Myeloma

Abstract

In the last decade, several significant advances in myeloma therapy have occurred with the pace of change accelerated with the introduction of new anti-myeloma agents. The approach to the treatment of multiple myeloma has become more complex with an array of therapeutic options, including autologous stem cell transplantation, non-myeloablative allogeneic transplantation, and new therapeutic agents such as thalidomide, bortezomib, and lenalidomide. High-dose chemotherapy followed by autologous stem-cell transplantation has emerged as the most effective approach to achieve high complete response rates and thereby improve the long-term overall survival. The majority of the patients, however, will develop progressive disease within several years. For patients who are not suitable candidates for high-dose chemotherapy due to advanced age or poor performance status conventional chemotherapy has remained the most common treatment with a median overall survival of 3 years. Treatment options for patients with relapsed or refractory disease are limited. The major obstacle to successful treatment of these patients is the development of drugresistant disease. The analysis of genetic rearrangements in monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma by the use of cytogenetics and molecular cytogenetics has contributed significantly to our understanding of the development of clonal plasma cell disorders. Modern techniques such as fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH) have revealed chromosomal abnormalities in virtually all patients with multiple myeloma and most patients with MGUS