| BackgroundRecently, many trials had shown the efficacy of bortezomib-based therapy in the treatment of patients with newly diagnosed multiple myeloma. However, to date, no sufficient clinical data confirm that bortezomib could effectively reverse renal function in myeloma patients with renal dysfunction. Currently, there is still no simple, convenient, and effective monitoring of quantitative indicators for myeloma kidney disease monitoring and treatment assessment. In recent years, studies have shown that the plasma/serum miRNA as a new cycle biomarker. Thus, we study the expression of serum miR-21in patients with myeloma nephropathy in order to assess the significance of myeloma nephropathy.In recent years, the outcome of multiple myeloma has been improved, thanks to thalidomide, lenalidomide, bortezomib. These novel agents has been applied as firstline therapy. Meanwhile, many questions remains answered urgently:Whether first-line treatment strategy with thalidomide in patients with newly diagnosed multiple myeloma correlates with postrelapse survival rate? Is lenalidomide more efficacy than thalidomide? Would continuous treatment strategy (the same novel agents used during induction and maintenance phase) induce survival advantage?We used meta-analysis to solve these questions.Section one. The efficacy of bortezomib in the treatment of myeloma nephropathy.Objective:To evaluate the effect of bortezomib-based chemotherapy in the treatment of myeloma patients with renal dysfunction. And, to explore the association of serum miRNA-21with myeloma nephropathy.Methods:A total of68cases of newly diagnosed myeloma patients (37cases with normal renal function,31cases of renal dysfunction) were enrolled to accept PAD regimen, while the other73newly diagnosed myeloma patients (41cases with normal renal function,32cases of renal dysfunction) were enrolled to accept VADT chemotherapy. The outcomes were response rates, progression-free survival, overall survival and adverse reactions and other aspects. And, we also evaluate the level of serum miR-21expression levels.Results:1. A total of60cases of myeloma patients were suitable for evaluating reversal rate, there are16cases (26.7%) patients who had renal dysfunction reversed. In the bortezomib group (PAD group),10of24(41.7%) cases had renal function reversed, significantly higher than that in the non-bortezomib group (VADT group)(3/36,16.7%)(RR,0.42, P=0.047).2. Among the many factors, univariate regression analysis showed that e-GFR≥30mL/min (RR=0.21, P=0.012) and bortezomib based therapy (RR=0.42, P=0.047) indicates that patients could reverse the possibility.3. In patients with or without renal dysfunction, bortezomib based therapy improved progression free survival.4. The levels of serum miRNA-21expression (1.63±0.12) in newly diagnosed myeloma patients with normal renal function was significantly lower than those with renal abnormalities (2.55±0.13)(P<0.01), but higher than thosel in the normal control group (0.49±0.10)(P<0.01).5. The level of miRNA-21expression with renal insufficiency not reversed (1.81±0.17) was significantly higher than that of renal function reversal (1.04±0.14)(P=0.01).6. Univariate regression analysis showed that the relative levels of serum miRNA-21expression correlated positively with estimated glomerular filtration rate (cGFR)(R2=0.85, P<0.01).In conclusion:1. Bortezomib based chemotherapy was more effective to reverse renal function than that in conventional chemotherapy in myeloma patients with renal dysfunction.2. The level of serum miRNA-21expression correlated with renal function of myeloma patients.Section two. Meta-analysis of anti-myeloma drug treatment strategyObjective:To assess the effects of thalidomide used as firstline treatment on postrelapse survival, the impact of continuous antimyeloma novel agents treatment strategy on overall survival, whether lenalidomide is more potent than thalidomide. Methods:To investigate the effect of novel agents in the treatment of newly diagnosed patients with multiple myeloma, we performed a meta-analysis of randomized controlled trials (RCTs). A comprehensive literature search (Medline, Embase, the Cochrane controlled trials register and the Science Citation Index) was undertaken.Results.1. Sixteen trials were identified, covering a toltal of6097subjects, andJPRS data were available from eight trials. The summary hazard ratios (HR)(thalidomide v control) of all those trials for PRS was1.23[95%CI,1.05to1.45].2. Indirection comparison of lenalidomide versus thalidomide maintenance after ASCT showed a PFS benefit (hazard ratio (HR)0.75,95%confidence interval (CI)[0.67,0.85], P<0.001) but no survival difference (HR0.83,[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 (HR0.53,95%CI [0.46,0.60], P<0.001). 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), indicating that the discontinuation rate from thalidomide trials seems to be higher than that from lenalidomide trials.3. Compared with conventional chemotherapy, continuing bortezomib treatment strategies can significantly prolong autologous stem cell transplant patients, overall survival (HR=0.8095%CI [0.64,0.99](P=0.04)); while thalidomide or lenalidomide continuous treatment strategies did not significantly prolong overall survival in patients with myeloma.Conclusion1. Thalidomide exposed upfront correlated with shorter PRS, which partially compensated for prolonged initially PFS.2. Indirection evidence shows that lenalidomide used as the first-line treatment for newly diagnosed patients with multiple myeloma had a significant advantage of PFS.3. Compared with conventional chemotherapy, bortezomib treatment strategies used as first-line treatment for newly diagnosed myeloma could prolong overall survival. |
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