The following is the first in a series of articles intended to provide readers with
answers to general questions submitted to the IMF Hotline. In this issue,
Dr. Robert A. Kyle, Chairman of the IMF Scientific Advisory Board and principal investigator of Mayo Clinic’s myeloma program, defines
Nonsecretory multiple myeloma is characterized by the absence of an M (monoclonal) protein in both the serum and urine. It occurs in approximately 2% of all patients with myeloma. The M-protein is found in the cytoplasm of the plasma cells in about 85% of patients. In the remainder, no M-protein can be found in the cytoplasm and these patients have truly nonsecretory myeloma. Electron microscopy of the plasma cells shows the same features as found in plasma cells of patients with an M-protein in serum or urine.
The lack of an M-protein in the serum and urine in nonsecretory myeloma may be due to the inability of the plasma cells to excrete the M-protein, low synthetic capacity of M-protein formation, degradation of the M-protein within the plasma cell or rapid degradation of M-protein after secretion from the plasma cell. The diagnosis of nonsecretory myeloma depends upon the demonstration of an M-protein (kappa or lambda) in the cytoplasm of the plasma cells when using an immunohistochemical stain. This is necessary because metastatic cancer must be excluded before the diagnosis of nonsecretory myeloma is proven.
Patients with nonsecretory myeloma are approximately ten years younger than in typical myeloma. Anemia and elevation of serum calcium occur less frequently in nonsecretory myeloma. Kidney failure is much less common and is probably due to the absence of monoclonal light chains (Bence Jones protein) in the urine. The tumor cell mass is usually less than that found in multiple myeloma. Almost all patients have lytic bone lesions. The IgG, IgA and IgM values are usually reduced. The most common initial manifestation is bone pain. X-rays of the bone reveal lytic lesions. The diagnosis depends upon the demonstration of an excess of monoclonal (kappa or lambda) plasma cells in the bone marrow.
Patients with nonsecretory myeloma are treated in the same fashion as multiple myeloma. Patients younger that 70 years should consider an autologous stem cell transplant. Patients older that 70 years should be treated with melphalan and prednisone or a combination of alkylating agents. Response to therapy and relapse of patients with nonsecretory myeloma cannot be determined by changes in the M-protein levels. The response to therapy is manifested by a reduction in bone pain, improvements of the hemoglobin level, decrease in serum calcium if initially abnormal, reduction of extramedullary plasmacytomas if present, no increase in lytic bone lesions and a reduction in the bone marrow plasma cells.
Survival of patients with nonsecretory myeloma is similar to that of patients with multiple myeloma. One might anticipate a longer survival in the nonsecretory group because of the absence of renal insufficiency. However, the absence on an M-protein in the serum or urine may delay diagnosis until later in the course of the disease making survival shorter. Overall there is no difference in the survival of patients with nonsecretory myeloma compared with