Introduction: The phase III POLARIX study (NCT03274492) demonstrated the superiority of Polatuzumab vedotin (Pola) combined with rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) over R-CHOP, marking the first major advancement in over 20 years in first-line (1L) diffuse large B-cell lymphoma (DLBCL). Pola-R-CHP improves progression-free survival (PFS) while maintaining a comparable safety profile and reducing the need for subsequent therapy. Sustained efficacy observed in POLARIX 5-year follow-up supported Pola-R-CHP as a curative standard option in the 1L setting. Real-world data (RWD) on Pola-R-CHP use in individual countries has been published. We conducted a systematic literature review (SLR) to aggregate global RWD for Pola-R-CHP in 1L DLBCL to further inform decision-making.

Methods: Adhering to PRISMA and Cochrane guidelines, MEDLINE®, Embase® and Evidence-Based Medicine Reviews were searched from inception to 3rd June 2025, supplemented with searches of major conference proceedings and bibliographies of included publications. Eligible studies evaluated the effectiveness and safety of Pola-R-CHP treatment in adult patients with 1L DLBCL in real-world settings. Both single- and multi-arm studies were included if they specifically assessed patients treated with Pola-R-CHP in a distinct treatment arm. Studies with multiple Pola-based regimens were included if ≥80% of participants received Pola-R-CHP. Patient characteristics and outcomes were extracted and summarized across studies. Where applicable, overall rates were calculated across studies to report pooled proportions or percentages.

Results: Of the 1,433 citations screened, 34 publications, reporting 28 unique real-world studies, were eligible for inclusion. Thirty-two publications were conference abstracts and two were full-length articles. Studies spanned Asia (n=20), Europe (n=4), and North America (n=4), reporting a total of 2,813 1L DLBCL patients treated with Pola-R-CHP. Outcomes of interest were not consistently reported in all studies. Inter-study variability was noted in both baseline characteristics and outcome reporting, which should be considered when interpreting the outcome data.

Median age was reported in 20 studies, ranging from 56 to 84 years. In 2 studies, the median age was >80 years and subgroup data for patients aged >80 years were reported in 7 studies. In the 21 studies reporting International Prognostic Index (IPI) score, IPI was ≥2 in 78% (1,247/1,595) of patients. In the 17 studies reporting cell of origin from either immunohistochemistry or gene expression profiling, 33% of patients (443/1,337) were classified as germinal center B-cell-like (GCB), 56% (747/1,337) as non-GCB, 1% (16/1,337) as activated B-cell-like, and 10% (131/1,337) as unclassified. In the 19 studies reporting Ann Arbor stage, 13% (241/1,845) of patients were categorized as stage I/II and 81% (1,486/1,845) of patients as stage III/IV. Two studies had a follow-up of <6 months, while the remaining 13 studies had a follow-up >6 months, including 3 studies with a follow-up exceeding 12 months. The objective response rate (ORR) for patients receiving Pola-R-CHP was 92% (1,294 responses of 1,411 patients across 19 studies). The complete response (CR) rate was 80% (1,144 responses of 1,438 patients across 22 studies), while the CR rate for patients aged >80 years was 74% (53 complete responses of 72 patients across 4 studies).The 12-month PFS rate for patients receiving Pola-R-CHP was 84% (773 patients event-free of 925 patients across 7 studies). Among patients aged >80 years, the overall 12-month PFS rate was 68% (34 patients event-free of 50 patients across 2 studies). Overall survival (OS) data were sparse (n=4 studies) due to insufficient follow-up. In 13 studies reporting adverse events (AEs), findings were consistent with POLARIX data. The most common AEs were all-grade neutropenia (35%, 138/391 across 6 studies), all-grade anemia (32%, 115/363 across 5 studies), and all-grade infections (27%, 96/352 across 5 studies). No quality-of-life data were reported.

Conclusion: This SLR analyzing currently available RWD addressing the safety and effectiveness of Pola-R-CHP for 1L DLBCL aligns with results from the POLARIX trial. Despite study and reporting heterogeneity, response rates and PFS are consistent, as are outcomes in patients older than 80 years, supporting the use of this regimen in patients with newly diagnosed DLBCL.

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2025
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