A New Insight about Multiple Myeloma

Abstract

Malignant myeloma (MM) is the second most common hematologic malignancy in the United States. Malignant plasma cells in multiple myeloma are usually limited to the bone marrow, although circulating malignant cells are detectable in many cases. Like normal plasma cells, the neoplastic plasma cells in myeloma secrete immunoglobulins. Because the plasma cell expansion is clonal, the malignant plasma cells secrete identical immunoglobulins, all sharing the same sequence and length (the specific sequence is unique and will vary from patient to patient). When the number of malignant plasma cells is high enough, a corresponding paraprotein can be detected as a discrete band on a diffusely stained (polyclonal) background when serum is analyzed by protein electrophoresis (serum protein electrophoresis [SPEP]). Electrophoresis has enabled early detection of monoclonal proteins in asymptomatic people. SPEP is often ordered in the workup of anemia, unexplained proteinuria, and neuropathy. The workup also often includes a bone marrow biopsy, which is examined for the level of plasma cell proliferation and light chain immunotype. Most people with an incidentally discovered paraprotein and small clonal plasma cell expansion live for years or decades with a slowly increasing monoclonal burden, but without development of overt myeloma. This state is termed monoclonal gammopathy of undetermined significance (MGUS). It is accepted that essentially all MM originates in MGUS, but most MGUS cases do not progress to MM, even after decades. MGUS is found in 5% to 10% of the general population by age 60 years; the subsequent incidence increases 1% per year Criteria for diagnosing MGUS, MM, and an intermediate state, “smoldering multiple myeloma” (SMM) have been developed by the International Myeloma Working Group (IMWG) and are set forth in the National Comprehensive Cancer Network (NCCN) Guidelines for Multiple Myeloma, version 5.2022 (at NCCN.org).