Combination Therapy for Multiple Myeloma: How Far Have We Come?

Multiple myeloma (MM) is a malignant neoplasm of plasma cells that constitutes 1% of all cancers and 10% of hematologic neoplasms. MM is the second most common hematologic malignancy after nonHodgkin’s lymphoma. It is estimated that 21,700 new cases of MM (approximately 12,190 men and 9,510 women) will be diagnosed during 2012 in the United States, and approximately 10,710 individuals (6,020 men and 4,690 women) will die of the disease [1]. The five-year survival rate for patients with MM is 40%, with younger patients showing higher survival rates than the elderly. However, MM still remains incurable and emergence of drug-resistance is considered to be one of the major causes of relapsed or refractory disease. Research in the last decade has shed new light on the biology of MM and the importance of the bone marrow microenvironment in supporting MM cell growth, survival, and therapy resistance. In addition, significant insight has been gained into the role of natural killer (NK) cells in myeloma progression and the existence of MM cancer stem cells (CSCs) has been established. Hence, with increased understanding of the MM disease and a novel armamentarium of molecularly targeted therapeutic agents, are we are close to overcoming the challenge of relapse in MM?