Treatment of patients with multiple myeloma: an overview of systematic reviews

Individual studies rarely provide definitive answers to questions related to the effects of treatments. Whether the treatment is associated with more good than harm is best answered by considering the totality of evidence on the topic through the methodology of systematic reviews. The objective of this overview is to summarize all existing systematic reviews on treatments in multiple myeloma (MM), which accounts for 14% of new cases of hematological malignancies each year. Therefore, MEDLINE and the Cochrane Database of Systematic Reviews were systematically searched to identify systematic reviews of interventions. Data were extracted on patients, interventions, control and outcomes. Methodological quality of the systematic reviews was assessed using the AMSTAR assessment tool. Eleven systematic reviews on treatment of MM were included in the overview. Ten addressed seven unique questions and also performed a meta-analysis. One addressed 21 clinical questions related to treatment decisions in myeloma. The quality of systematic reviews varied. The results from the overview show that early treatment does not offer survival benefit. Thalidomide is associated with improved survival when added to standard chemotherapy regimens as induction or maintenance therapy but at the expense of an increased risk of serious adverse events, such as venous thromboembolism. High-dose therapy with single autologous hematopoietic stem cell transplant (AHCT) is associated with superior event-free but not overall survival compared to chemotherapy. Tandem AHCT does not prolong survival but is associated with better event-free survival in comparison to single AHCT. In addition, combination treatment with bisphosphonates reduces pathological vertebral fractures and pain, but does not prolong survival. We found no systematic review evaluating the effects of other novel agents, such as bortezomib or lenalidomide, as single agents or in combinations. Several key clinical questions have been successfully answered by conducting systematic reviews. However, currently many questions of importance for the management of patients with myeloma continue to be dealt with in individual studies instead of synthesized evidence. There is urgent need to perform research synthesis of data related to the effects of novel agents.