Objective: To evaluate the efficacy of first-line Pola-R-CHP therapy in patients with high-risk diffuse large B-cell lymphoma (DLBCL) at a single center in China under real-world conditions. Methods: We retrospectively analyzed newly diagnosed CD20-positive DLBCL patients who received first-line Pola-R-CHP between November 1, 2022, and January 31, 2025. Primary endpoint was complete response (CR) rate after 6 cycles; secondary endpoints included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: Among 52 patients (median age 62 years, 50.0% male), 90.2% had stage III-IV disease, 90.7% IPI ≥2, 39.2% ECOG ≥2, and 42.3% non-GCB subtype. Next-generation sequencing (NGS) was performed in 30.2% patients (37.5% TP53 alterations), 64.2% met POLARIX trial eligility criteria. Post-treatment CR was 47.5%, ORR 82.5%. Key CR subgroups: IPI 0-1: 100% vs. IPI 2-5: 45.2%, P=0.04, GCB: 52.6% vs. non-GCB: 50.0%, P=1.00, TP53-altered: 42.9% vs. wild-type: 77.8%, P=0.30, POLARIX-eligible: 45.8% vs. ineligible: 50.0%,P=0.79. For POLARIX-eligible subgroup (90.0% stage III-IV, NGS rate 23.5%, 62.5% TP53-altered): GCB CR: 53.0% vs. non-GCB: 50.0%, P=1.00, TP53-altered: 60.0% vs. wild-type: 100%, P=0.46. For POLARIX-ineligible sungroup (88.2% stage III-IV, NGS rate 38.9%, 28.6% TP53-altered): GCB CR: 50% vs. non-GCB: 33.3%, P=0.62, TP53-altered: 0% vs. wild-type: 53.8%, P=0.47. At median follow-up of 15.6 months, entire cohort: 12 month PFS was 92.3%, OS 94.3%, IPI 0-1: both PFS and OS were 100%, IPI 2-5: PFS 89.6%, OS 90.9%, POLARIX-eligible: 12 month PFS 85.0%, OS 93.1%, POLARIX-ineligible: PFS 86.7%, OS 90.5%. Conclusion: This real-world study demonstrated significantly lower CR rates with first-line Pola-R-CHP compared to POLARIX. This disparity likely reflects both the enrichment of high-risk patients (90.2% stage III-IV, 39.2% ECOG ≥ 2) and constrained PET/CT availability (predominant reliance on CT for response assessment), illustraiting the impact of socioeconomic factors in resource-limited settings where Pola use clusters within advanced populations. Caution is warranted due to potential selection bias, small sample size, and limited follow-up, extended studies are needed.

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2025
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