Real-world outcomes of polatuzumab vedotin plus R-CHP versus R-CHOP in newly diagnosed diffuse large B-cell lymphoma: A propensity-matched analysis.

e19087 Background: Polatuzumab vedotin plus R-CHP (Pola-R-CHP) was approved as frontline therapy for diffuse large B-cell lymphoma (DLBCL) in 2022 after demonstrating improved progression-free survival compared with R-CHOP in the POLARIX trial, without a significant overall survival (OS) benefit at initial or long-term follow-up. However, real-world safety and survival outcomes in routine clinical practice, particularly among patients with higher comorbidity burden, remain incompletely characterized. Methods: A retrospective cohort study was conducted using the TriNetX research network. Adult patients with newly diagnosed DLBCL receiving Pola-R-CHP or R-CHOP were identified. Cohorts were balanced using 1:1 propensity score matching for age, sex, race/ethnicity, baseline comorbidities, and available laboratory data (standardized mean differences <0.1). The primary outcome was OS. Secondary outcomes included sepsis, tumor lysis syndrome (TLS), anemia, and major cardiovascular events. Kaplan–Meier, Cox regression, and logistic regression were used. Results: After matching, 533 patients were included in each group. Mean age was similar between Pola-R-CHP and R-CHOP (67.6 ± 12.4 vs 66.4 ± 14.4 years), with 54.4% male patients. Baseline comorbidities were common and well-balanced, including diabetes (~22%), chronic kidney disease (~13%), heart failure (~8%), and chronic lung disease (~7%). Mean baseline LDH levels were identical between groups (329 ± 294 U/L; 91% availability). Overall survival was comparable between Pola-R-CHP and R-CHOP, with no statistically significant difference on time-to-event analysis (HR 0.92; 95% CI 0.74–1.15; p = 0.47) and overlapping Kaplan–Meier curves. Anemia occurred at similar rates in the Pola-R-CHP and R-CHOP groups (36.8% vs 34.5%; OR 1.10; 95% CI 0.86–1.42; p = 0.44), with no difference on time-to-event analysis (HR 1.02; 95% CI 0.83–1.25; log-rank p = 0.86). Major cardiovascular events were also comparable (11.3% vs 10.0%; OR 1.14; 95% CI 0.76–1.72; p = 0.53; HR 1.04; 95% CI 0.71–1.54; log-rank p = 0.83). TLS occurred numerically less frequently with Pola-R-CHP compared with R-CHOP (3.9% vs 5.4%), though this difference was not statistically significant (OR 0.71; 95% CI 0.40–1.27; p = 0.25; HR 0.67; 95% CI 0.38–1.18; log-rank p = 0.16). Sepsis occurred at similar rates in both groups (13.5% vs 11.8%; OR 1.17; 95% CI 0.77–1.78; p = 0.46), with no difference on time-to-event analysis (HR 1.09; 95% CI 0.74–1.61; log-rank p = 0.66). Conclusions: In this large, real-world propensity-matched cohort of patients with newly diagnosed DLBCL, Pola-R-CHP demonstrated overall survival and safety outcomes comparable to R-CHOP in a population with substantial comorbidity burden. These findings support the feasibility of Pola-R-CHP in routine clinical practice and extend the external validity of POLARIX trial results.