The objective of the study was to investigate the effects and safety of novel agents such as
bortezomib and
lenalidomide in the treatment of newly diagnosed patients with
multiple myeloma. We performed a comprehensive meta-analysis of randomized controlled trials (RCTs). An initial search yielded 627 citations, of which 10 RCTs enrolling 4534 patients met the inclusion criteria. The addition of
bortezomib to first-line
therapy significantly prolonged overall survival (OS) (hazard ratio [HR], 0.75 [0.65, 0.87], p < 0.001). On the other hand, the addition of
lenalidomide had no impact on survival (HR, 0.88 [0.65, 1.20], p = 0.42). Both
lenalidomide and
bortezomib consistently improved progression-free survival (PFS) compared with conventional
therapy alone. The corresponding HRs were 0.65, 95% confidence interval (CI) [0.55, 0.77] (p < 0.001) for
bortezomib and 0.48, 95% CI [0.42, 0.55]; (p < 0.001) for
lenalidomide, respectively. Some of the increased adverse events reported were
herpes zoster (relative risk [RR], 3.64 [2.23, 5.94], p < 0.001),
peripheral neuropathy (RR, 3.59 [1.89, 6.83], p < 0.001) and gastrointestinal effects (RR, 2.19 [1.37, 3.50], p = 0.001) among patients receiving
bortezomib, and gastrointestinal effects (RR, 2.36 [1.33, 4.17], p = 0.003) and thromboembolic events (RR, 2.55 [1.48, 4.38], p < 0.001) among patients receiving
lenalidomide. Interestingly, treatment with
bortezomib seemed to be associated with a lower rate of treatment related mortality (RR, 0.39 [0.18, 0.85], p = 0.02). An increased incidence of
second primary cancers was observed in the
lenalidomide group (RR 2.61 [1.60, 4.27], p < 0.001). In summary,
bortezomib improved OS, and both
lenalidomide and
bortezomib consistently improved PFS of patients with newly diagnosed myeloma when it was added to standard
therapy.