Multiple myeloma (MM) is a clonal plasma cell malignancy with a highly heterogeneous genetic background, characterized by bone marrow (BM) plasmacytosis, production of monoclonal proteins, osteolytic bone lesions, hypercalcemia, renal disease, anemia, and immunodeficiency. Several advances in diagnosis and treatment have been achieved during the past years. More sensitive imaging techniques, cytogenetic evaluations, and novel assays to measure paraprotein levels help to discern monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM (SMM) from MM, and thereby enable the selection of patients who need treatment. Progress in our understanding of MM pathogenesis has led to the identification of new therapeutic targets. The introduction of derived agents, including thalidomide, bortezomib, and lenalidomide, into conventional chemotherapeutic regimens has fundamentally changed treatment strategies in MM during the last decade and steadily improved patient outcome.
Multiple myeloma (MM) is the second most common hematologic malignancy in the United States. Age-adjusted incidence and mortality rates of MM in the United States are 5.6 and 3.6 cases per 100,000 persons per year, respectively.1-3 MM is a disorder of terminally differentiated B lymphocytes, called plasma cells, that are preferentially located within the bone marrow and secrete monoclonal immunoglobulin (IgG in about 60%, and IgA in about 20%) or light chains (κ or λ). Deregulated tumor cell growth and paraprotein production induce myelosuppression, bone destruction and hypercalcemia, immunodeficiency, hyperviscosity, and renal failure. Other plasma cell disorders include monoclonal gammopathy of undetermined significance (MGUS), smoldering MM (SMM), and solitary plasmacytoma. MGUS and SMM, also referred to as indolent or asymptomatic MM, are characterized by the absence of symptoms and require regular follow-up but no treatment. The rare solitary plasmacytoma occurs as a single lesion and benefits from local therapies. Recent advances in the diagnostic workup helped to distinguish these forms of disease from symptomatic MM, and thereby helped to select patients who needed treatment. Improvements have been achieved also by the identification of tumor microenvironment-directed agents, including thalidomide, bortezomib, and lenalidomide. Their inclusion in current MM treatment regimens has extended median overall survival (OS) from 3 to at least 7 years, especially in the younger patient population.4 In addition, novel effective supportive therapies have improved patients’ quality of life.
Despite therapeutic advances, MM ultimately relapses and remains an incurable disease. Current research goals aim to further increase our knowledge, to identify additional targeted therapies, and to define patient-specific sequence and combination regimens in order to reduce adverse effects and improve response rates. Here, we summarize recent advances in both diagnosis and treatment strategies.
|Title||Expiration Date||CME Credits|
|Advances in Next-Generation Sequencing in Precision Oncology: Solid Tumors||Jul 27, 2016||2.0|
|Cancer Summaries and Commentaries™: Update from Chicago: Advances in the Treatment of Hematologic Malignancies||Jul 31, 2016||2.5|