Pola-R-CHP versus R-CHOP in Newly Diagnosed Diffuse Large B-Cell Lymphoma: A Systematic Review of Efficacy, Safety, and Patient Selection

Background The combination of polatuzumab vedotin with rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) has emerged as a potential frontline therapy for diffuse large B-cell lymphoma (DLBCL). This systematic review synthesizes the current evidence comparing the efficacy and safety of Pola-R-CHP versus the standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen. Methods We systematically searched PubMed and Science Direct from inception to January, 2026 for studies reporting on Pola-R-CHP versus R-CHOP in previously untreated DLBCL. Data on study characteristics, efficacy outcomes, safety, and biomarker analyses were extracted. The risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool for randomized trials. Results 23 studies were included, comprising the pivotal phase 3 POLARIX trial, its subgroup and long-term follow-up analyses, real-world evidence, and biomarker studies. Pola-R-CHP demonstrated a consistent and significant improvement in progression-free survival (PFS) compared to R-CHOP (hazard ratio (HR) range: 0.64–0.77), with a 5.8% absolute PFS benefit at 5 years. Overall survival (OS) data showed a positive but non-significant trend (5-year HR: 0.85). The benefit was most pronounced in higher-risk patients, including those aged ≥ 70, with International Prognostic Index (IPI) scores 3–5, and those with activated B-cell (ABC) subtype DLBCL (PFS HR: 0.34). The safety profile was manageable but distinct, with a higher incidence of febrile neutropenia requiring granulocyte colony-stimulating factor (G-CSF) prophylaxis but fewer dose reductions. Patient-reported outcomes indicated no detriment in quality of life. Conclusion Pola-R-CHP represents a significant advance in the first-line treatment of DLBCL, offering a superior PFS benefit over R-CHOP with a manageable toxicity profile. Its use is most favorable in higher-risk and biologically defined patient subgroups. Future research should focus on long-term OS and validating predictive biomarkers for precision-based patient selection.