R-CHOP With or Without Molecule-Directed Agents in Patients with Diffuse Large B-Cell Lymphoma

In a review of trials on the addition of molecular targeted agents (MTAs) to the rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, and prednisone (R-CHOP) treatment regimen for patients with diffuse large B-cell lymphoma (DLBCL), researchers found that the combination regimen had slightly better progression-free survival (PFS). However, they also had higher toxicity and odds of adverse events (AEs) for patients with DLBCL. The study was published in Annals of Hematology.

According to lead author, Guillermo Villacampa, the team observed an improved rate of progression-free survival (PFS) in younger patients with DLBCL on the MTA and R-CHOP combination regimens.

The final analysis included seven randomized clinical trials that compared R-CHOP and MTAs versus R-CHOP alone in 3,255 patients with untreated DLBCL. The investigators used fixed and random effects models to calculate pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CI). The primary outcomes were progression-free survival (PFS), overall survival, and adverse events (AEs).

Three different types of MTAs were combined with R-CHOP in the trials: bortezomib, ibrutinib, and lenalidomide. According to the authors, R-CHOP plus MTA had a slightly superior PFS (HR = 0.86; 95% CI, 0.76–0.98) compared to R-CHOP alone. No variations were found based on the subtype of DLBCL. As noted, younger patients had a significantly better PFS with R-CHOP plus MTA (HR = 0.72; 95% CI, 0.56–0.93), but this benefit was lost in patients older than 60 years (HR = 0.96). Lastly, R-CHOP plus MTAs had increased odds of developing serious AEs (OR = 1.46; 95% CI, 1.11–1.91).

The authors concluded that, despite encouraging findings from preliminary trials on R-CHOP plus MTAs in patients with untreated DLBCL, the pooled results demonstrate only a slightly improved PFS over traditional R-CHOP, as well as a unfavorable increase in toxicity. Although, they noted, the improved outcomes in younger populations may be worth further investigation.