Safety And Efficacy Of Anti-PD-1/PD-l1 Antibodies In Patients With Relapsed Or Refractory Diffuse Large B-Cell Lymphoma:a Meta-Analysis

Background: For patients with relapsed/refractory diffuse large B-cell lymphoma(RR DLBCL)who are ineligible for ASCT due to age,comordidity and other factors,there are currently no standard treatment regimens and few treatment options available.Programmed death receptor-1/programmed death receptor ligand-1 blockades are effective in the treatment of many malignant settings such as non-small cell lung cancer,melanoma and renal cancer.Currently,two PD-1blockades have been approved by the FDA and four more domestically made PD-1blockades been approved by the SFDA for use in patients with R/R c HL.At present most published clinical trials of PD-1/PD-L1 blockades in DLBCL are in phase 1phaes 2 and no satisfied therapeutic effects were observed in these trials.The safety and efficacy of PD-1/PD-L1 blockades in R/R DLBCL was analysed in this article.Methods: To evaluate the safety and efficacy of PD-1/PD-L1 blockades for RR DLBCL,we searched relative published clinical trials in Pubmed,EMbase,the Cochrane Library and CNKI and extracted data on treatment outcome and related adverse events.Data processing was performed using Rev Man 5.3 software.Overall response rate(ORR),6-month progression-free survival(PFS)and 6-month overall survival(OS)as efficacy indexes and the incidence of all grade and grade ≥3 adverse events(AEs)as safety indexes were analysed and the types of adverse events were summarized.Q and I2 statistical methods were adopted to evaluate the heterogeneity across studies.Results: Nine clinical trials in eight studies were included and 405 patients were enrolled totally.The pooled ORR rate,CRR rate were 0.32(95%CI 0.17,0.50)and0.19(95%CI 0.11,0.30)respectively.The pooled 6m-PFS rate and 6m-OS rate were0.38(95%CI 0.19,0.60)and 0.65(95%CI 0.49,0.78)respectively.The pooled all grade and grade ≥3 AEs rate were 0.75(95%CI 0.62,0.85)and 0.43(95%CI 0.22,0.66)respectively.It was found that fatigue is the most common AEs in any grades and neutropenia is the most common grade ≥3 AEs.No treatment-related deaths was found in each study.Conclusion: In general,no promising therapeutic effects of PD-1/PD-L1 blockades were achieved on certain types of RR DLBCL in the included trials.However,according to the molecular characteristics of tumors,good therapeutic effects may be achieved when PD-1/PD-L1 blockades applied to some specific types like primary mediastinal large B cell lymphoma.Meanwhile,PD-1/PD-L1 blockades were found to be safe and well tolerated when used in RR DLBCL...