BACKGROUND: Diffuse large B-cell lymphoma (DLBCL), the most common non-Hodgkin's lymphoma subtype, relapses or becomes refractory (R/R) in 40 % of cases after initial treatment. Among the second-line treatments for these patients is CAR T-cell therapy, which is considered the gold standard and treatment better than SCT. For these patients, polatuzumab vedotin in combination with bendamustine and rituximab (Pola-BR) is a novel treatment. The main goal of our research is to evaluate Pola-BR's efficacy in R/R DLBCL patients. METHODS: We followed PRISMA criteria for conducting this systematic review and meta-analysis. A search was conducted from the start until May 2024 using the Cochrane Library, PubMed, and clinicaltrials.gov. Studies included randomized-controlled trials, observational studies, and single-arm studies assessing Pola-BR efficacy in R/R DLBCL patients. The overall response rate (ORR), partial response (PR), and complete response (CR) were the main outcomes. Using random-effect models, statistical analysis was carried out on OpenMeta[Analyst] software leading to pooled risk ratios with 95 % confidence intervals (CIs). RESULTS: Eight studies with 398 patients were present in our study. The studies were of high quality, with pooled analysis showing a significant ORR of 52.6 % (95 % CI: 43.6 - 61.6 %), CR of 34.3 % (95 % CI: 23.5 - 45.0 %), and PR of 15.5 % (95 % CI: 8.7 - 22.3 %). Significant hematologic toxicities were observed, the most common being, neutropenia, thrombocytopenia, neuropathy, and anemia. CONCLUSION: Pola-BR is an effective option for advanced R/R DLBCL but poses significant hematologic toxicity, requiring careful management. Further high-quality randomized trials are needed to better understand and evaluate Pola-BR's success. To fully assess its effectiveness, comparisons with non-cell therapies are essential.