Background

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma and disproportionately affects elderly individuals. Polatuzumab vedotin (Pola) has shown promise in improving outcomes in DLBCL therapy. However, the effectiveness and safety of Pola-based regimens in previously untreated elderly patients with DLBCL (EPU-DLBCL), especially those defined as unfit or frail remain unclear. Treatment response may vary across geographic regions, healthcare systems, and clinical practice settings. Therefore, a systematic review and meta-analysis was conducted to synthesize the available evidence and explore potential heterogeneity.Method

We systematically searched PubMed, EMBASE, the Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and CBM databases from inception to June 25, 2025. Studies were included if they involved EPU-DLBCL (aged ≥60 years) receiving Pola-based regimens. Eligible study designs included randomized or non-randomized controlled trials, single-arm trials, cohort studies, and case series, reported as original articles, short reports or letters, and abstracts. The primary outcome was complete response rate (CRR) assessed at the end of treatment. Secondary outcomes include overall response rate (ORR), 1- and 2-year cumulative progression free survival (PFS) rates, overall survival (OS) rates, and their corresponding median survival time. Subgroup analyses were performed on primary outcome based on study design (clinical trials vs. observational studies), age groups (≥65, ≥70 and ≥80 years), treatment regimen (Pola-R-CHP vs. non–Pola-R-CHP) and geographic region (China vs. non-China). Meta-analysis was conducted using R software with a random-effects model.Results

A total of 19 studies involving 1,015 patients were included, reported across 26 articles. The median age ranged from 67.5-84.3 years, and 51% of the patients were male. Among the 13 studies (575 patients) reported cell of origin, the GCB subtype accounted for 47.1%, while the non-GCB subtype accounted for 45.7%. Of the 15 studies (753 patients) reported IPI scores, 90.0% had IPI of 2-5, whereas 8.4% had IPI of 0-1. The Pola-based treatment regimens included Pola-R-CHP (58.5%), Pola-R-Glofit (14.9%), Pola-Mosun (10.6%), Pola-ZR (5.3%), Pola-R2 (3.5%), Pola-Mosun-CHP (2.6%) etc.

Fifteen studies (655 patients) reported CRR, with a pooled CRR of 79% (95% CI: 71%–86%). In subgroup analyses, clinical trials (8 studies, 534 patients) showed a CRR of 73% (95% CI: 62%–84%), while observational studies (7 studies, 121 patients) showed a relatively higher CRR of 87% (95% CI: 77%–95%). Among age subgroups, patients aged ≥65 years (9 studies, 373 patients) had a CRR of 86% (95% CI 0.79-0.92), those aged ≥70 years (5 studies, 188 patients) and ≥80 years (3 studies, 61 patients) had a CRR of 85% (95% CI: 78%–91%) and 90% (95% CI: 71%–100%) respectively. For patients defined as unfit or frail (3 studies, 45 patients), CRR was 86% (95% CI 0.66-0.99). Among the treatment regimens, Pola-R-CHP (8 studies, 450 patients) yielded a CRR of 81% (95% CI: 73%–89%), while non–Pola-R-CHP regimens (7 studies, 150 patients) showed a CRR of 75% (95% CI: 57%–90%).For geographic region, CRR was 83% (95% CI: 70%–94%) in 5 studies from China (68 patients) and 81% (95% CI: 75%–87%) in 9 studies from non-China regions (531 patients).The pooled ORR from 11 studies (646 patients) was 90% (95 CI: 82%–96%). The median follow-up time ranged from 2.1-40 months. The 1- and 2-year PFS rate was 92% (95% CI: 86%-99%, 5 studies, 467 patients) and 88% (95% CI: 79%-98%, 3 studies, 415patients) respectively. The 1- and 2-year OS rate were both 96% (95% CI: 92%-100%, 5 studies, 467 patients; and 95% CI: 91%-100%, 2 studies, 377 patients, respectively). Median PFS and OS were not reached at the time of analysis.Conclusion

Pola-based regimens presented favourable responses in EPU-DLBCL. Encouraging PFS and OS further demonstrated the durable clinical benefits, suggesting sustained long-term responses among these patients. Subgroup analyses revealed consistent effectiveness. The Pola-R-CHP regimen showed better response, supporting its use as a frontline option in this population. The meta-analysis is ongoing; safety and long-term survival data will be updated in due course.

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2025
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