Bortezomib and thalidomide for the first‑line treatment of multiple myeloma

Multiple myeloma is a cancer of a type of white blood cell (plasma cell) in the bone marrow. In people with multiple myeloma, a single plasma cell becomes cancerous to form a myeloma cell, which begins to multiply. These abnormal plasma cells, or myeloma cells, build up in the bone marrow, reducing the space available for making normal white cells, red cells and platelets. Normal blood cells are responsible for fighting infections, carrying oxygen around the body and blood clotting. Myeloma cells produce large amounts of 1 type of abnormal antibody, which does not work properly and is not able to fight infection. Symptoms and clinical features of multiple myeloma include fatigue, bone pain and/or fracture, anaemia, infections, M-protein in serum and/or urine, and hypercalcaemia. The origin of multiple myeloma is unknown and malignant cells display a variety of cytogenetic abnormalities. Multiple myeloma is the second most common haematological cancer in the UK. In England and Wales there are approximately 3,600 new diagnoses recorded annually. In 2007, most diagnoses were recorded in people aged 75 to 79 years. Multiple myeloma is about 1.5 times more common in men than in women, and twice as common in people of African or Caribbean descent. In the UK, the estimated lifetime risk of developing multiple myeloma is 1 in 148 for men and 1 in 186 for women. There are currently between 10,000 and 15,000 people living with multiple myeloma in the UK.

Multiple myeloma remains an incurable disease, with an average survival of 4 to 6 years, but it can be treated with a combination of supportive measures and chemotherapy. The aim of treatment is to extend the length and quality of life by alleviating symptoms, controlling disease and minimising adverse effects. Survival after diagnosis can vary from months to more than 10 years. Factors affecting survival and outcome include burden of disease, type of cytogenetic abnormality, age and performance status, and response to treatment.

In England and Wales, the choice of first-line treatment (that is, treatment for treatment-naïve patients) depends on a combination of factors. Most people with multiple myeloma are not able to withstand intensive treatment, such as high-dose chemotherapy with stem cell transplantation, because of their age, other health problems or poor performance status. These people are offered single-agent or combination chemotherapy, which is less intensive. Typically, combination therapies include chemotherapy with an alkylating agent (such as melphalan or cyclophosphamide) and a corticosteroid (such as prednisolone or dexamethasone). More recent treatment options include drugs such as thalidomide and bortezomib. The main objective of first-line therapy is to achieve a period of stable disease (termed the plateau phase) for as long as possible, thereby prolonging survival and maximising quality of life. After initial treatment, most people usually experience a period of remission, but almost all relapse eventually, and some have disease that does not respond (is refractory) to treatment.