Efficacy and safety of pola-based therapy in molecularly defined high-risk DLBCL: A retrospective analysis of real-world data

Abstract Introduction Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma. Despite improved prognosis with R-CHOP, patients with high-risk features (≥2 extranodal sites, DEL, CD5+, EBV+, TP53 mutations) have poor outcomes. These patients exhibit low complete response rates and high recurrence risks when treated with R-CHOP, underscoring the urgent need for more effective therapeutic strategies. The POLARIX trial showed polatuzumab vedotin (Pola), an anti-CD79b ADC, has demonstrated a significant improvement in progression-free survival (PFS) . However, it enrolled few high-risk patients and used strict criteria, limiting generalizability to real-world populations. Real-world data on Pola-based regimens in high-risk DLBCL remain limited. Based on real-world data, this study retrospectively evaluates the efficacy and safety of Pola-based regimens specifically among molecularly and pathologically defined high-risk previously untreated DLBCL patients, providing evidence to support precision treatment decision-making. Methods A retrospective analysis was conducted on previously untreated DLBCL patients aged ≥18 years who were treated at The First Affiliated Hospital of Chongqing Medical University between April 2024 and June 2025. All patients received at least 3 cycles of Pola-based regimens, with the vast majority administered Pola-R-CHP, consisting of polatuzumab vedotin (1.8 mg/kg, intravenous [IV], day 1); rituximab (375 mg/m², IV day 1); cyclophosphamide (750 mg/m², IV, day 1); doxorubicin (50 mg/m², IV, day 1); and prednisone (100 mg,oral, days 1–5), repeated every 21 days. The primary endpoint was complete response rate (CRR) at the end of treatment (EOT). Secondary endpoints included overall response rate (ORR), incidence of adverse events (AEs) during treatment, progression-free survival (PFS), and overall survival (OS). A multivariable Cox regression–based risk scoring model was constructed based on four clinical features: cell-of-origin subtype (ABC), ≥2 extranodal sites, gastrointestinal tract involvement, and bone marrow involvement. Each variable contributed 1 point to a composite risk score. Patients were classified as high-risk (score ≥2) or low-risk, and their association with CR was analyzed using Cox proportional hazards modeling. Results 40 patients were included (median age 64, range 23–87; 70% female). According to the Hans classification, 60% of patients were classified as activated B-cell-like (ABC) lymphoma. Patients with International Prognostic Index (IPI) scores of 3–5 accounted for 57.5%, and 80.0% of Ann Arbor stage was III-IV. 72.5% of patients had extranodal involvement, 52.5% with ≥2 extranodal sites. The proportions of DEL, CD5-positive, EBV-positive, and TP53-mutated patients were 42.5%, 42.5%, 20%, and 27.5%, respectively. The median treatment cycles was 5 (range: 3–8). Among 34 EOT-evaluable patients, CRR was 64.7% and ORR 97.1%. At EOT, the CRR and ORR among patients with ≥2 extranodal sites were 63.2% and 94.7%, respectively. Corresponding values were 85.7% and 100% for DEL patients, 57.1% and 100% for EBV-positive patients, 58.8% and 94.1% for CD5-positive patients, and 70% and 100% for TP53-mutated patients. The median follow-up duration was 4 months (range: 1–13). Only two patients experienced disease progression at 3 and 7 months, respectively, and no deaths were observed over the study period. A composite score based on ABC subtype, extranodal site involvement (≥2), gastrointestinal tract involvement, and bone marrow involvement (1 point each, high-risk defined as score ≥2) showed a significant association with achieving CR at EOT. High-risk patients, as defined by this score, exhibited a significantly greater likelihood of attaining CR (HR = 3.02, 95% CI: 1.13–8.04, P = 0.0274). The most common AEs was gastrointestinal reaction (60%), followed by myelosuppression (12.5%), most of which were grade 1–2. The most common grade 3–4 AEs were myelosuppression (5%) and neutropenia (5%). No participants discontinued treatment because of adverse events. Conclusion Our findings indicate that Pola-based regimens exhibit high response rates and favorable safety profiles in newly diagnosed DLBCL patients with high-risk features in real world settings. Prospective studies with larger cohorts are needed to further validate these observations.