Pathophysiological Underpinnings of Multiple Myeloma Progression

BACKGROUND: Multiple myeloma (MM) is a malignant neoplasm of plasma cells that accumulate in the bone marrow. Myeloma is characterized by skeletal destruction, renal failure, hypercalcemia, and anemia. Currently, there is no cure, though recent understanding of the bone marrow microenvironment and the cytogenetics involved in MM are leading to improved and individualized treatment strategies, leading to longer periods of remission and improved survival rates. OBJECTIVES: To review MM pathophysiology, genetic issues, other risk factors, and the steps of disease progression. This section will address diagnosis, staging, classification, and disease complications, as well as the roles of cytogenetic abnormalities and the bone marrow milieu. SUMMARY: In MM, malignant plasma cells in the in the bone marrow produce large quantities of monoclonal protein (M protein) leading to stimulation of osteoclasts. This increase in osteoclast activity leads to bone resorption and destruction, causing painful bone lesions and hypercalcemia. Myeloma cells also crowd out other normal bone marrow cells, which leads to a plethora of complications, including renal insufficiency, anemia, infection, and clotting disorders. Updated standards of diagnosis, staging, and classification of MM have recently been developed. The International Staging System (ISS) categorizes myeloma patients into 1 of 3 groups based on serum albumin and beta2-microglobulin blood tests. Genetic mutations leading to chromosomal translocations and deletions play a key role in the progression to active, malignant MM. Cytogenetic testing allows physicians to appropriately diagnose and treat patients' specific to their unique presentation of disease. CONCLUSIONS: The future of treating the myeloma patient is progressing at a fast and positive pace. Identification and treatment of comorbid conditions are leading to improvements in quality of life. Identification of potential therapeutic targets in the bone marrow microenvironment is leading to the development of therapies that are changing the standard of care for MM patients.