Combination of novel molecular targeted agent plus R-CHOP-based regimen versus R-CHOP alone in previously untreated diffuse large B-cell lymphoma (DLBCL) patients: a systematic review and meta-analysis.

The addition of molecular targeted agents (MTAs) to R-CHOP has been one of the main focuses of research in patients with DLBCL. Despite encouraging preliminary results, recent randomized controlled trials (RCT) have not shown a definitive benefit over standard R-CHOP. Here we conducted a systematic review and meta-analysis to investigate the impact of this strategy. A systematic literature review was conducted to identify RCT that evaluated the addition of MTA to R-CHOP-based regimen versus R-CHOP alone in previously untreated DLBCL patients. Fixed and random effects models were used to estimate pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CI). Progression-free survival (PFS), overall survival, and adverse events (AE) were analyzed. A total of seven RCT including 3,255 patients with DLBCL met the eligibility criteria. Three different types of MTAs (bortezomib, ibrutinib, and lenalidomide) were investigated in combination with R-CHOP. Overall, R-CHOP plus MTA showed a slightly better PFS (HR=0.86; 95% CI: 0.76-0.98). No differences were observed according to the cell of origin subtype of DLBCL. Interestingly, patients younger than 60 years had a significantly better PFS with R-CHOP plus MTAs (HR=0.72; 95% CI: 0.56-0.93), while no benefit was observed in patients older than 60 years (HR=0.96). The combination strategy showed higher odds to develop serious AEs (OR= 1.46, 95% CI 1.11-1.91). R-CHOP plus MTA seems only to slightly improve PFS in patients with DLBCL, particularly in younger patients. An increase in toxicity was observed in comparison to R-CHOP.

Automated summary

A systematic review and meta-analysis found that adding molecular targeted agents to R-CHOP in DLBCL patients may only slightly improve progression-free survival (PFS). Younger patients may benefit more, but with a higher rate of adverse events.