Comparative real-world safety outcomes of Pola-R-CHP versus R-CHOP in high-grade diffuse large B-cell lymphoma (DLBCL): A TriNetX study.

Abstract

e19000 Background: The POLARIX trial established polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) as a potential new standard of care for previously untreated intermediate- and high-risk DLBCL, demonstrating a significant 5-year progression-free survival benefit over rituximab, cyclophosphamide, doxorubicin, oncovorin, and prednisone (R-CHOP), with similar overall survival and safety profiles. However, the generalizability of these trial findings to diverse patient populations and routine clinical practice remains to be fully elucidated. Methods: We conducted a retrospective propensity score-matched (PSM) study using the TriNetX Global Collaborative Network database. We identified adults (≥18 years) with DLBCL/high-grade lymphoma (ICD-10: C83.3) who received either Pola-R-CHP (n=1,045) or R-CHOP (n=18,382). We applied 1:1 PSM for age, sex, race, comorbidities, and transplantation status. The primary outcome was all-cause mortality. Secondary outcomes included hematologic toxicities, infections, cardiomyopathy, and healthcare utilization. Hazard ratios (HR) were calculated with 95% confidence intervals (95% CI), and Kaplan–Meier survival curves were generated. Results: Median follow-up was 347 days for Pola-R-CHP and 365 days for R-CHOP after PSM for demographics, comorbidities, and baseline disease characteristics. After matching, 1,045 patients were included in each cohort. At the 1-year median follow-up, the Pola-R-CHP cohort had a lower all-cause mortality than the R-CHOP cohort (7.0% vs. 13.3%; HR 0.595, 95% CI 0.445–0.794, P<0.001). Kaplan-Meier analysis also showed the survival benefits of Pola-R-CHP. Neutropenia was lower with Pola-R-CHP than with R-CHOP (31.1% vs. 37.5%; P = 0.05), as was the rate of thrombocytopenia (13.2% vs. 16.3%; P = 0.068), but neither reached statistical significance. Peripheral neuropathy was higher with Pola-R-CHP than with R-CHOP (22.2% vs. 19.1%; HR 1.28, 95% CI: 1.049 –1.571, p=0.015). No statistically significant between-groups differences were observed in cardiomyopathy, hospitalization rates, emergency room visits, disease progression, anemia, sepsis, or pneumonia. Conclusions: This real-world PSM study demonstrated significantly reduced all-cause mortality in Pola-R-CHP vs. R-CHOP. While many toxicities were similar, Pola-R-CHP showed a higher rate of peripheral neuropathy. These findings suggest that Pola-R-CHP is a better upfront option with improved survival benefits and no new safety concerns in patients with DLBCL.