B cell function and risk of progression in smouldering myeloma

Multiple myeloma (MM) is a cancer of the blood and bone marrow which affects 24,000 patients in the UK at any one time. Patients with MM have an abnormal growth of plasma cells in their bone marrow. These cancerous plasma cells grow in an uncontrolled manner and can cause symptoms such as kidney failure, bone pain and fractures, and anaemia caused by low red blood cells. Although many new treatments exist, MM remains incurable. MM starts as a pre-cancerous condition called smouldering myeloma, where abnormal plasma cells are detected in the bone marrow, but patients do not have symptoms. Currently these patients are not treated but are monitored as many will progress to symptomatic disease over time and need chemotherapy, however others will not. Although there is interest in treating these patients to see if we can delay progression to active MM, we do not have a full understanding of why some people progress, and others don't, to predict which patients will need treatment. In addition, if we understand the factors that contribute to disease progression from smouldering myeloma we hope that targeted treatments could be given to stop active myeloma developing.

We now understand that progression of pre-malignant conditions to cancer occurs when cancer cells have escaped from the control of immune cells, and that these immune cells play a part in controlling the smouldering plasma cells in patients who do not progress. But we do not understand the functions of the different types of immune cells here. Most research has focussed on a type of white blood cells called T cells which can kill cancer cells. B cells are another type of immune cell, that fight infection by making antibodies. We know that the B cells in MM patients are often defective, and do not make normal levels of antibodies in response to infection or vaccination. Thus MM patients often get frequent infections. Plasma cells, which are the cancer cell in myeloma, are also related to B cells. We do not...