Five RCTs were included in the review (1,566 patients including four trials, where reported). All trials used intention-to-treat analysis but none adequately reported the amount and pattern of data censoring. Randomisation was adequate in two trials, and allocation concealment was adequate in three trials. Baseline comparability was adequate in four trials, but blinding was not adequate in most trials.
Bortezomib in combination with melphalan and prednisone (one RCT): One RCT reported that compared with melphalan and prednisolone/prednisone, bortezomib in combination with melphalan and prednisone was more effective in terms of overall survival, time to progression and the proportion of participants who achieved a complete response or achieving a partial response.
Thalidomide in combination with melphalan and prednisone (three RCTs): Compared with melphalan and prednisolone/prednisone, thalidomide in combination with melphalan and prednisolone/prednisone was more effective in terms of overall survival (two RCTs) and progression-free survival (two RCTs). Thalidomide in combination with melphalan and prednisolone/prednisone was also associated with a significant increase in the proportion of participants achieving complete response (three RCTs). No significant heterogeneity was observed for these outcomes.
Thalidomide in combination with cyclophosphamide and attenuated dexamethasone (one RCT): One RCT reported that compared with melphalan and prednisolone/prednisone, thalidomide in combination with cyclophosphamide and attenuated dexamethasone was more effective in terms of complete response. Data on survival outcomes did not meet the inclusion criteria.
In terms of adverse events, one RCT reported that bortezomib therapy was associated with a significant increase in grade 3 (severe) adverse events. The most commonly reported adverse event associated with the use of thalidomide was peripheral neuropathy. A range of adverse events (including thrombosis, embolism, somnolence, infections and constipation) were reported as being significantly increased in the thalidomide-containing arms of some trials.
Results for other outcomes were also reported.