Thalidomide (T) and lenalidomide (R) have been used as first-line therapy for previously untreated myeloma. However, direct head-to-head comparison between them is lacking. We performed an indirect meta-analysis to assess the treatment effects of lenalidomide- versus thalidomide-based regimens using common comparators. A comprehensive literature search was undertaken. The initial search yielded 1345 citations, of which 11 randomized controlled trials (RCTs) enrolling 4162 patients met the inclusion criteria. Indirect comparison of lenalidomide versus thalidomide maintenance after autologous stem cell transplant (ASCT) showed a progression-free survival (PFS) benefit (hazard ratio [HR] 0.75, 95% confidence interval [CI] [0.67, 0.85], p < 0.001) but no survival difference (HR 0.83, [0.63, 1.09], p = 0.19) when using observation/placebo as the common comparator. Similarly, the indirect comparison of melphalan-prednisone plus lenalidomide followed by lenalidomide maintenance (MPR-R) versus melphalan-prednisone-thalidomide induction followed by thalidomide maintenance (MPT-T) showed a statistically significant PFS advantage for MPR-R (HR 0.53, 95% CI [0.46, 0.60], p < 0.001), but no difference for overall survival (OS) (HR 0.97, [0.81, 1.17], p = 0.74). Additionally, the significant heterogeneity among pooled studies for the outcome of discontinuation rate due to treatment-related adverse events between MPT-T and MPR-R subgroups (p = 0.007) indicated that the discontinuation rate from thalidomide trials seems to be higher than that from lenalidomide trials. In conclusion, lenalidomide seems to be a more potent and less toxic agent than thalidomide in the treatment of patients with multiple myeloma. Further, a direct head-to-head trial comparing lenalidomide versus thalidomide is clearly warranted.
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.
PurposeThe use of carfilzomib/pomalidomide single-agent or in combination with other agents in patients with refractory/relapsed multiple myeloma (RRMM) was not clearly clarified in clinical practice. We sought to compile the available clinical reports to better understand the efficacy and safety of carfilzomib (CFZ) and pomalidomide (POM).ResultsBased on our research criteria, we identified 37 prospective studies that evaluated 1160 patients. Analysis of subgroup differences between carfilzomib single-agent and CFZ/DEX dual combination showed significantly(P < 0.001, I2 = 96.3%), suggesting the overall response rate (ORR) of 66% attained from CFZ/DEX dual combination seemed to be higher than that of 28% from carfilzomib single-agent. And, the same trend favoring CFZ/DEX dual combination was found in ≥VGPR and CBR analysis. The ORR of 31% attained from POM/DEX dual combination was superior to that of 19% from pomalidomide single-agent(P < 0.001, I2 = 94.4%). And, the same trend favoring POM/DEX dual combination was found in ≥VGPR and CBR analysis. However, the ORR of 83% attained from POM/BOR/DEX triplet combination was superior to that of 31% from POM/DEX dual combination(P < 0.001, I2 = 99.1%). And, the same trend favoring POM/BOR/DEX triplet combination was found in ≥VGPR analysis.MethodsWe searched published reports including carfilzomib and (or) pomalidomide therapy for RRMM who had received bortezomib and (or) lenalidomide.ConclusionPomalidomide/Carfilzomib plus dexamethasone seemed to attain a superior response rate compared with pomalidomide/carfilzomib single-agent. Furthermore, the combination of pomalidomide, bortezomib and dexamethasone resulted in a much higher response rate compared with pomalidomide plus dexamethasone regimen. These results needed more validation in future trials.
To examine the role of novel agents such as bortezomib, lenalidomide, and thalidomide as continuous therapy (induction and consolidation/maintenance) in the treatment of newly diagnosed patients with multiple myeloma, we carried out a meta-analysis of randomized-controlled trials. A comprehensive literature search (Medline, Embase, the Cochrane controlled trials register, and the Science Citation Index) was performed. The initial search yielded 849 citations, of which 11 randomized-controlled trials enrolling 4775 patients fulfilled the inclusion criteria. Continuous addition of bortezomib to conventional therapy before and after autologous stem cell transplantation prolonged overall survival significantly: the summary hazard ratio was 0.80, 95% confidence interval [0.64, 0.99] (P=0.04). Continuous therapy with novel agents consistently improved progression-free survival (PFS) compared with therapy with conventional agents alone. For those patients ineligible for a transplant, the summary hazard ratios for PFS were 0.69 [0.56, 0.85] (P<0.001) for continuous thalidomide therapy and 0.47 [0.33, 0.68] (P<0.001) for continuous lenalidomide therapy; for those patients ineligible for a transplant, the summary hazard ratios for PFS were 0.68 [0.59, 0.79] (P<0.001) for continuous thalidomide therapy and 0.72 [0.61, 0.85] (P<0.001) for continuous lenalidomide therapy. In summary, continuous therapy with novel agents improved PFS consistently, and bortezomib may improve the overall survival of patients with newly diagnosed myeloma when it is added to standard transplantation therapy continuously.
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