Chemoimmunotherapy with RCHOP is the standard frontline treatment for DLBCL based on a 5-year overall survival (OS) of almost 60%. Depending on baseline risk factors, 20%-30% of patients will relapse or have refractory disease. As such, intensified regimens such as RCHOP14 are being used. But evidence of effectiveness and toxicity of RCHOP14 versus RCHOP21 is scarce.
In this systematic review and meta analysis conducted per Cochrane guidelines we included all RCTs addressing clinical outcomes and toxicity of dose intensification (RCHOP 14) versus RCHOP 21 regimens in patients with DLBCL. Data were pooled and reported as hazard ratio (HR) or risk ratio (RR) under a random-effects model and reported with 95% confidence intervals (95% CIs).
We included four RCTs enrolling 2956 patients. Pooled results showed no difference between RCHOP 14 and RCHOP 21 regimens for OS (HR 0.92, 95% CI 0.77 to 1.09) and progression free survival (PFS) (HR 0.96, 95% CI 0.82 to 1.12).RCHOP 21 regimen achieved higher rates of complete responses (CR) compared to RCHOP 14(RR 1.15, 95% CI 1.06 to 1.25; I2 0%, 4 RCTs). There were no differences between RCHOP 14 and RCHOP 21 regimens for pooled estimates of treatment related mortality (RR 1.49, 95% CI 0.51 to 4.30), febrile neutropenia (RR 0.76, 95% CI 0.32 to 1.80), neutropenia (RR 0.78, 95% CI 0.36 to 1.67), thrombocytopenia (RR 1.18, 95% CI 0.54 to 2.58), cardiotoxicity (RR 1.33, 95% CI 0.09 to 19.59), and peripheral neuropathy (RR 1.26, 95% CI 0.90 to 1.79). Overall methodological quality of included studies was moderate due to publication bias and imprecision.
The results of this meta-analysis showed that RCHOP14 regimen in patients with DLBCL achieved lower CR rates compared to RCHOP21. However, both regimens were similar in terms of PFS, OS and grade 3 or 4 toxicities. These results suggest that the efficacy and safety of both regimens are comparable, and that R-CHOP14 remains a viable option in patients who prefer a shorter therapy course. Further analyses are needed to assess the cost differences between both chemotherapies.
Clinical trial identification
Legal entity responsible for the study
Moffitt Cancer Center.
A. Ausekar: CEO, major shareholder and member of the Board of Directors: Personome Life Sciences. K. Purnapatre: Head of research: Personome Life Sciences. J. Scheiber: Founder and major shareholder: Biovariance; Scientific advisor: Personome Life Sciences. All other authors have declared no conflicts of interest.