Pola-R-CHP as frontline therapy for diffuse large B-cell lymphoma: a systematic review and meta-analysis of randomized trials and real-world evidence.

Pola-R-CHP regimen is the new standard of care for untreated diffuse large B-cell lymphoma (DLBCL) patients, following the POLARIX trial. This study evaluates whether clinical trial (RCT) efficacy and safety are reproducible in real-world evidence (RWE) settings. This systematic review and meta-analysis compared outcomes between RCTs and RWE studies. Primary endpoints were complete response (CR) rate, progression-free survival (PFS), and overall survival (OS). Meta-regression explored heterogeneity using age, International Prognostic Index (IPI), and activated B-cell-like (ABC) subtype as moderators. Data from 2 RCTs and 10 RWE studies (3472 patients) were integrated. The pooled CR rate was 78% (95% CI: 74-82%), with RWE studies showing a significantly higher CR (80%) than RCTs (69%, P < 0.001). The pooled 1-year PFS was 85%, significantly higher in RWE (86%) than RCTs (81%, P = 0.02). Pooled 1-year OS was 91%, with no significant difference between RWE (90%) and RCTs (94%, P = 0.35). Despite high heterogeneity (I2 74-91%), meta-regression confirmed that age, IPI score, and ABC subtype did not significantly influence treatment effects, though trends for improved CR and PFS were noted. In conclusion, this meta-analysis confirms that Pola-R-CHP outcomes in real-world practice are consistent with, and occasionally exceed, those observed in clinical trials. Despite inherent heterogeneity in RWE, these findings support Pola-R-CHP as a robust frontline therapy for a broad DLBCL population, regardless of baseline clinical characteristics.