Therapy strategies for multiple myeloma: current status

Multiple myeloma (MM) is characterized by infiltration of bone marrow with a clone of neoplastic plasma cells. Impaired hematopoiesis and reduced production of functional immunoglobulins, as well as the induction of pathognomonic osteolytic lesions primarily contribute to the morbidity of patients with MM. Conventional chemotherapy is the treatment of choice for older patients, whereas those under 60 years benefit significantly from high-dose therapy followed by stem-cell rescue. The use of tandem transplantation, developed to further escalate the conditioning dose, has achieved additional improvement in survival. Interferon-a and glucocorticoids are effective as maintenance measures in MM but remain controversial because of their associated high costs and considerable toxicity. The resurrection of an old drug, thalidomide, for the therapy of MM and the development of potent immunomodulatory derivatives are highly promising new treatments that target MM cell-host interactions and the bone-marrow microenvironment, as well as the myeloma cell itself. The importance of the use of bisphosphonates for the prevention or amelioration of skeletal complications and hypercalcemia is well established. New generations of bisphosphonates show potent antitumor activity, again emphasising the importance of targeting the microenvironment of the plasma-cell clone.