| Objective:To assess the clinical efficacy of rituximab for diffuse large B cell lymphoma treatment through systemic review and meta analysis.Method:We searched Pubmed、 Cochrane Library、 CBM、 CNK、VIP、 Tsinghua Tongfang、Wanfang database and handsearched some related Chinese Journals. Randomizede controlled trials or Non-randomized controlled trials of rituximab therapy in diffuse large B cell lymphoma were included. Used RevMan5.1software to Meta analyse the data, the relative risk for binary data was estimated and pooled and hazard ratios for time-to-event data was also. By used the chi-square test to analyze the heterogeneity and the fixed effect model on the research results of Meta analysis. Evaluation of outcome indices included OS, EFS, PFS, FFS, OR, CR.Result:A total of Nineteen RCTs and N-RCTs were identified including 3380patients with diffuse large B cell lymphoma, in which seven RCTs were rituximab in first-line treatment; two RCTs were rituximab in first-line maintenance therapy; four RCTs and N-RCTs were rituximab in salvage therapy; six N-RCTs were rituximab treatment in diffuse large B cell lymphoma subtypes (GCB type, non-GCB). The results of meta-analysis were listed as follows:1、Patients treated with rituximab combined with routine chemotherapy had statistically significantly better OS [HR=0.69,95%CI (0.58-0.82), p<0.0001]、 EFS [HR=0.61,95%CI (0.52-0.70),p<0.00001]、 PFS [HR=0.53,95%CI (0.44-0.64), p<0.0001], OR[RR=1.22,95%CI (1.10-1.35), p=0.0001] and CR [RR=1.20,95%CI (1.10-1.31), p<0.0001] than patients treated with routine chemotherapy.2、(1) Patients treated with maintenance rituximab had no statistical significance in OS[HR=0.96,95%CI (0.63-1.47), P=0.85], but statistically significantly in FFS [HR=0.63,95%CI (0.44—0.90), P=0.009] compared to the observation arm. Subgroup analysis, only in induction therapy which did not use rituximab, FFS was statistically significant [HR=0.45,95%CI (0.29-0.71), P=0.004].(2) High-dose chemotherapy followed by autologous stem cell transplantation as induction therapy with rituximab maintenance therapy compared to observation arm, EFS was no statistically significant [HR=0.69,95%CI (0.43—1.12) P=0.14]. Either aa IPI2, aaIPI3, or CRu/PR subgroup, EFS were not statistically significant [HR=0.63,95% CI(0.35-1.14),P=0.13; HR=0.83,95%CI (0.35-1.94), P=0.66; HR=0.96,95%CI (0.50-1.83), P=0.90]; respectively], only CR subgroup, EFS had statistical significance [HR=0.43,95%CI (0.21-0.89), P=0.02]3^1) Rituximab combined with high-dose chemotherapy with autologous stem cell transplantation under salvage treatment for refractory or relapsed diffuse large B cell lymphoma compared with high-dose chemotherapy with autologous stem cell transplantation treatment, OSs PFS and OR had statistical significance [HR=0.71,95%CI (0.52-0.98), p=0.04; HR=0.72,95%CI (0.53-0.98), p=0.04; RR=1.36,95%CI (1.14-1.63), p=0.0007].(2) R-ESHAP immunochemotherapy as the salvage treatment for refractory or relapsed diffuse large B cell lymphoma, OS, PFS, OR were similar with ESHAP arm and had no statistical significance [HR=1.06,95%CI (0.66—1.70), p=0.80; HR=0.93,95%CI (0.55-1.58), p=0.80; RR=0.96,95%CI (0.70-1.31), p=0.78]4、 In GCB、 non-GCB two subtypes, rituximab combined with routine chemotherapy had compared with routine chemotherapy, OS and EFS had statistical significance [HR=0.55,95%CI (0.35-0.86), p=0.008; HR=0.49,95%CI(0.35-0.68), p<0.0001; HR=0.52,95%CI (0.33-0.82), p=0.005; HR=0.51,95%CI(0.35-0.76), p=0.0007; respectively]; OR had no statistical significance in GCB subset [RR=1.04,95%CI (0.94-1.15), p=0.47], but was statistically significant in non-GCB subset (RR=1.53,95%CI (1.231.90), p=0.0001]. In rituximab combined with routine chemotherapy group, OS、EFS、OR were no statistically significant between the GCB and non-GCB suubtype[HR=0.67,95%CI(0.42-1.06),p=0.09；HR=0.86,95%CI(0.53-1.39),p=0.54；RR=1.09,95%CI(0.99-1.19),p=0.08；respectively].In routine chemotherapy group,both improved OS、OR in GCB Subtype and were statistically signifiant[HR=0.59,95%CI(0.44-0.79),p=0.0005；RR=1.60,95%CI(1.29-1.99), p<0.0001；respectively], but EFS improved was not statistically signi]ficant[HR=0.77,95%CI(0.52-1.13),p=0.18]Conclusions:1、Rituximab combined with routine chemotherapy improves OS、EFS、 PFS、OR、CR, and confirmed that Rituximab combined with routine chemotherapy as the preferred first-line treatment of DLBCL2、Rituximab maintenance treatment for diffuse large B-cell lymphoma, OS and EFS were not statistically significant.Because of only included2RCTs, rituximab maintenance treatment of DLBCL whether benefit,still need to undertake a large number of prospective, randomized controlled study to provide the basis.3.Rituximab combined with high-dose chemotherapy with autologous stem cell transplantation under salvage treatment for refractory or relapsed di ffuse large B cell lymphoma,OS.PFS and OR were statistically signincant. R-ESHAP immunochemotherapy as salvage chemotherapy for relapsed or refractory diffuse large B cell lymphoom,OS、PFS and OR were similar with ESHAP and were no statistically significant.Because the included studies were less, methodological quality assessment were low and the ending evidence quality assessment were Very low, it still need to undertake a large number of prospective, randomized controlled study to provide the basis.4、 Both in GCE、 non-GCB subtypes, OS and EFS were statistically significant; as in rituximab combined with routine chemotherapy group, OS, EFS and OR were no significant difference between the GCB and non-GCB subtype. All of these suggest that rituximab improves the prognosis of a poor prognosissubtype of non-GCB. Because of the included studies were N-RCTs, methodological quality assessment were low and the ending evidence quality assessment were Very low, still need to undertake a large number of prospective, randomized controlled study to provide more favorable basis. |
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