Real-world comparative outcomes of pola-R-CHP versus R-CHOP in patients with diffuse large B-cell lymphoma

Abstract Introduction: The emergence of novel immunotherapies has transformed the treatment landscape for hematological malignancies such as diffuse large B-cell lymphoma (DLBCL). As these therapies become more widely adopted in clinical practice, comparative evidence is needed to inform treatment selection and guide patient care. Building upon the pivotal POLARIX trial (NCT03274492), we conducted a national, real-world analysis of clinical outcomes between patients with DLBCL who received either the novel Pola-R-CHP regimen (polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone) or the standard R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Methods: We conducted a retrospective cohort study using real-world data from the TriNetX United States Research Database, a federated network of de-identified electronic health records (EHRs) from over 70 healthcare organizations. The study period included all relevant data from August 1st, 2005, to August 1st, 2025, or a standard 20-year lookback period. Propensity score matching was used to adjust for confounders, and time-to-event analysis was performed using Cox proportional hazards models with additional Kaplan-Meier survival analyses where appropriate. Statistical significance was determined by p < 0.001. Our primary outcome was overall survival, and several additional secondary outcomes were explored. Results: 108,907 DLBCL patients were identified, of whom 753 were exposed to Pola-R-CHP only and 16,664 were exposed to R-CHOP only. Propensity score matching identified 752 patients per cohort thereafter. The Cox proportional hazards model demonstrated that DLBCL patients who received Pola-R-CHP had greater overall survival than those who received R-CHOP (HR 0.653, CI 0.512-0.832, p<0.0006). Median overall survival for R-CHOP was 153.8 months, whereas median overall survival for Pola-R-CHP was not met; however, median follow-up for Pola-R-CHP was 11.9 months, and for R-CHOP was 47.8 months. Furthermore, Pola-R-CHP recipients were less likely to progress to further lines of treatment (HR 0.560, CI 0.440-0.714, p<0.0001) at data cutoff. On secondary analysis, Pola-R-CHP was associated with lower rates of hospitalization (RR 0.654, CI 0.582-0.735), ICU admission (RR 0.582, CI 0.449-0.755), thrombocytopenia (RR 0.741, CI 0.620-0.885), all-cause heart failure (RR 0.699, CI 0.535-0.803), all-cause acute hypoxic respiratory failure (RR 0.605, CI 0.460-0.796), acute kidney injury (RR 0.621, CI 0.424-0.756), and all-cause encephalopathy (RR 0.547, CI 0.396-0.756). Conclusion: In this real-world, retrospective multi-cohort analysis, we report comparative outcomes associated with Pola-R-CHP versus R-CHOP in DLBCL. Most notably, Pola-R-CHP demonstrated superior overall survival and a lower likelihood of requiring further lines of therapy. As the integration of novel agents into these therapeutic regimens expands, ongoing evaluation of these analyses will be essential to inform treatment sequencing and optimize patient care.