Meta-analysis Of The Effect Of Anti-CD20 Monoclonal Antibody Maintenance Therapy On Survival Of Follicular Lymphoma Patients After Different First-line Induction Regimens

Objective:To evaluate the efficacy of rituximab maintenance(RM)on follicular lymphoma(FL)in terms of overall survival(OS),progression free survival(PFS),event free survival(EFS),safety and adverse events.Methods:Cochrane systematic review was made in this article.The following databases were searched:Cochrane Library,MEDLINE,Pub Med,EMBASE and China national knowledge internet(CNKI),Wanfang database,VIP database,manual retrieval of ASH meeting?other related journals,and all the included references as well as the published or unpublished randomized controlled trial(RCT)on the maintenance treatment of follicular lymphoma(FL),With PFS,OS,EFS and adverse reactions as the main evaluation indexes.Revman 5.3 software of Cochrane Collaboration Network was used to do Meta-analysis.Results:Fifteen trials including 2884 patients were analysed,all of which were randomized controlled trials.Among these studies,14 reported OS results,3for 3 year OS,9 for PFS,5for EFS,3 for grade 3-4 adverse events,7 for infection,5 for neutropenia,respectively.The results showed that compared with the observation arm,the OS of rituximab maintenance arm were statistically significant(HR=0.83,95%CI=0.73,0.73-0.94,P<0.05).The data of OS was divided into 4 subgroups.group A:RM 375mg/m~2,4 weekly infusions every 6 months;B:375mg/m~2,once every 2-3 months for 2 years;group C:chemotherapy±rituximab in the first-line induction;group D:rituximab for the first-line induction;The results were HR=0.77,95%CI=0.6-0.98,P<0.05 for group A;HR=0.9,95%CI=0.77-1.6,P>0.05 for group B;HR=0.78,95%CI=0.68-0.9,P<0.05 for group C;HR=0.65,95%CI=0.44-0.94,P<0.05 for group D,respectively.The difference between group C and group D was statistically significant,but there was no significant difference between group B and group C,indicating that either the first-line induction regimen was chemotherapy or rituximab single drug treatment,RM group was superior to the observation group in OS;RM schedule was 375mg/m~2,4 weekly infusions every 6 months,the OS results were statistically significant,but when RM schedule was 375mg/m~2,once every 2-3 months for 2 years,there was no statistically significant difference,suggesting that the administration of once every 2-3months may not improve OS.Patients received rituximab maintenance were significantly better than those in the observation arm in the terms of PFS and EFS(HR=0.58,95%CI=0.53-0.63,P<0.05;HR=0.57,95%CI=0.45-0.73,P<0.05).The results of grade 3-4 adverse events were RR=1.43,95%CI=1.05-1.95,P<0.05;the most common adverse reactions were infection and neutropenia,the statistical results were RR=1.44,95%CI=1.08-1.92,P<0.05;RR=2.38,95%CI=1.05-5.42,P<0.05,respectively.The differences were statistically significant,suggesting that the risk of adverse events was higher with MR groups.Conclusion:RM treatment can improve PFS,EFS and OS of FL patients,However,it should be noted that the regimen of once every 2-3 months may not improve the OS of patients.Either the induction regimen is chemotherapy or rituximab alone,RM can improve OS.However,for the question of whether different chemotherapy regimen affects the efficacy of RM or not,further researches will be needed to answer.Due to the lack of relevant data at present.RM would increase the incidence of adverse events,but most of them can be better controlled,so the efficacy of RM is definite.