Multiple myeloma is the most common primary cancer of the bones in adults, representing about 1% of all cancers diagnosed in the US in 2004, and 14% of all haematological malignancies. In the UK, multiple myeloma accounts for 1% of all new cases of cancer diagnosed each year.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatment in people with asymptomatic early stage multiple myeloma (stage I)? What are the effects of first-line treatments in people with advanced stage multiple myeloma (stages II and III)? What are the effect of salvage treatments, or supportive therapy, in people with advanced stage multiple myeloma (stages II and III)? We searched: Medline, Embase, The Cochrane Library and other important databases up to November 2004 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
We found 71 systematic reviews, RCTs, or observational studies that met our inclusion criteria.
In this systematic review we present information relating to the effectiveness and safety of the following interventions: allogenic transplant (non-myeloablative), autologous stem cell transplant (early or late transplantation, double or single, purging of), bisphosphonates, bone marrow stem cells, bortezomib, chemotherapy (combination, conventional dose, intermediate dose plus stem cell rescue, high-dose plus stem cell rescue), combination chemotherapy plus corticosteroids, deferred treatment (in stage I disease), early chemotherapy plus corticosteroids (in stage I disease), epoetin alpha, first-line treatments, infection prophylaxis, interferon, maintenance therapy (in advanced multiple myeloma), melphalan (normal dose, high dose before autologous stem cell transplantation, plus total body irradiation), optimum priming regimen, peripheral blood stem cells, plasmapheresis, salvage therapy regimens, single-agent chemotherapy (adding prednisolone), single-agent chemotherapy (bendamustine, melphalan, cyclophosphamide, lomustine, carmustine) with or without corticosteroid (prednisolone, dexamethasone), syngeneic transplantation, and thalidomide (and derivatives).
Multiple myeloma is a neoplastic proliferation of plasma cells, mainly within the bone marrow, causing anaemia, renal dysfunction, infections and bone lesions. Monoclonal protein is found in serum and/or urine in 97% of people.
Early chemotherapy plus corticosteroids have not been shown to improve survival in people with asymptomatic, early stage multiple myeloma.
In people with advanced multiple myeloma, combination chemotherapy or single agent chemotherapy plus prednisolone improves survival more effectively than single agent chemotherapy alone, and adding corticosteroids to combination chemotherapy is more effective still
High or intermediate dose chemotherapy with bone marrow or peripheral blood stem cell rescue improves progression free and overall survival compared with conventional dose chemotherapy.
Syngeneic (from a twin) or autologous stem cell transplantation may increase event free, but not overall, survival if given early rather than late.An optimum priming regimen with stem cell factor may increase the yield of CD34+ cells for transplantation, but increases the risk of adverse effects.
Very high dose melphalan may increase overall survival and have fewer adverse effects compared with high dose melphalan plus total body irradiation.
Adding interferon to chemotherapy increases response rates and progression free, but not overall, survival, but increases toxicity.
We don't know which are the most effective salvage regimens,or if thalidomide increases survival, but bortezomib may increase response rates and overall short term survival.
In people with advanced disease, bisphosphonates reduce skeletal fractures and pain, epoetin alpha may improve anaemia, prophylactic treatment with antibiotics and immunoglobulin may reduce infections, and plasmapheresis may improve renal function when added to forced diuresis plus chemotherapy.
However, we don't know whether any of these treatments improve survival, and they may increase adverse effects.