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Cochrane Database of Systematic Reviews

Early versus deferred treatment for early stage multiple myeloma

Overview of attention for article published in Cochrane database of systematic reviews, January 2003
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Early versus deferred treatment for early stage multiple myeloma
Published in
Cochrane database of systematic reviews, January 2003
DOI 10.1002/14651858.cd004023
Pubmed ID

Yulong He, Keith Wheatley, Axel Glasmacher, Hamish Ross, Benjamin Djulbegovic


Early stage multiple myeloma (MM) represents about 20% of MM. Most of the patients are asymptomatic. Thus, it is far less dramatic than advanced disease and may require different treatment strategies. For these patients, it is not clear whether it is better to start chemotherapy right after the diagnosis or to delay the treatment until symptoms become obvious as the disease progresses. To identify and synthesize all available research evidence on whether early treatment intervention results in improved clinical outcomes when compared with observation alone. The main outcomes of interest that were examined included mortality, disease progression, response rate, and toxicity of early treatment. Searches of the following electronic databases were undertaken: MEDLINE, EMBASE, CANCERLIT, LILLIACS and Cochrane Database of RCTs. We have recently compiled a comprehensive database of RCTs in myeloma. This search was updated and supplemented by hand-search of abstracts from main society meetings such as the ASH (American Society of Hematology), ASCO (American Society of Clinical Oncology), and EHA (European Haematology Association). In addition, we compared our list with a list of RCTs maintained by the Oxford Clinical Trial Service Unit. Randomized controlled trials (RCT) with a parallel design that compared early versus deferred treatment of patients with early stage multiple myeloma based on Durie-Salmon (D-S) staging system. We also considered those trials that did not define early stage myeloma according to D-S staging system, but enrolled patients according to clinical uncertainty about the benefits of immediate intervention. Data synthesis was performed for all studies and according to the defined quality criteria. The first reviewer and the contact reviewer of this proposal independently extracted data. Disagreement was resolved by consensus. Revman software (ver 4.1) was used to combine results from all studies and expressed as an overall odds ratio or Peto's Odds Ratio, with 95% confidence interval. Three trials were included with a total of 131 patients in each of the early treatment and deferred treatment groups. Early MM is asymptomatic stage I in these trials. All trials used standard Melphalan treatment but not stem cell transplantation. No statistically significant heterogeneity among the studies was detected. Beneficial effects of early treatment were seen in delay of myeloma progression (Peto's OR = 0.16, 95% CI: 0.09-0.29), and reduced vertebral compression (OR = 0.18, 95%CI: 0.02-1.59, NNT = 23, 95% CI: an NNT of 11, via infinity, to an NNH of 50). No significant effects on mortality and response rate were seen (Peto's OR = 1.11, 95% CI: 0.67-1.84, and OR = 0.63, 95% CI: 0.33-1.23, respectively). Early treatment may increase the risk of acute leukemia (Peto's OR = 3.20, 95% CI: 0.55-18.73, NNH = 44, 95% CI: an NNT of 63, via infinity, to an NNH of 15). Early treatment of early stage multiple myeloma inhibits disease progression, and may reduce vertebral compression. However, early treatment may increase the risk of acute leukemia. However, the data on vertebral compression and leukaemic transformation may not be interpretable due to very small numbers. Based on the current evidence, mortality and response rate are not significantly affected by introducing early treatment in the progression of myeloma. However, it is quite possible that the lack of beneficial effects of early intervention in myeloma is a false negative result due to the paucity of the existing evidence. In addition, data on quality of life and toxicity were sparsely reported adding to additional difficulties about management decisions in early stage myeloma.

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Mendeley readers

The data shown below were compiled from readership statistics for 116 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 3 3%
Malaysia 1 <1%
Spain 1 <1%
Netherlands 1 <1%
Unknown 110 95%

Demographic breakdown

Readers by professional status Count As %
Researcher 15 13%
Other 12 10%
Student > Bachelor 10 9%
Student > Master 9 8%
Student > Ph. D. Student 7 6%
Other 18 16%
Unknown 45 39%
Readers by discipline Count As %
Medicine and Dentistry 34 29%
Nursing and Health Professions 10 9%
Psychology 7 6%
Economics, Econometrics and Finance 4 3%
Biochemistry, Genetics and Molecular Biology 4 3%
Other 11 9%
Unknown 46 40%