Pola-R-CHP versus R-CHOP in newly diagnosed diffuse large B-cell lymphoma: a systematic review of efficacy, safety, and patient selection

Introduction: 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.Materials and methods: We systematically searched PubMed and Science Direct from inception to September, ۲۰۲۵ 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 ۲ (RoB ۲) tool for randomized trials.Results: ۲۳ studies were included, comprising the pivotal phase ۳ 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: ۰.۶۴-۰.۷۷), with a ۵.۸% absolute PFS benefit at ۵ years. Overall survival (OS) data showed a positive but non-significant trend (۵-year HR: ۰.۸۵). The benefit was most pronounced in higher-risk patients, including those aged ≥۷۰, with International Prognostic Index (IPI) scores ۳-۵, and those with activated B-cell (ABC) subtype DLBCL (PFS HR: ۰.۳۴). 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.Introduction: 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. Materials and methods: We systematically searched PubMed and Science Direct from inception to September, ۲۰۲۵ 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 ۲ (RoB ۲) tool for randomized trials. Results: ۲۳ studies were included, comprising the pivotal phase ۳ 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: ۰.۶۴-۰.۷۷), with a ۵.۸% absolute PFS benefit at ۵ years. Overall survival (OS) data showed a positive but non-significant trend (۵-year HR: ۰.۸۵). The benefit was most pronounced in higher-risk patients, including those aged ≥۷۰, with International Prognostic Index (IPI) scores ۳-۵, and those with activated B-cell (ABC) subtype DLBCL (PFS HR: ۰.۳۴). 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.

کلیدواژه ها:

Diffuse Large B-Cell Lymphoma ، DLBCL ، Polatuzumab Vedotin ، R-CHOP ، Pola-R-CHP ، Systematic Review ، Frontline Therapy