Final results of JCOG0601 randomized trial of R-CHOP versus CHOP combined with dose-dense rituximab for diffuse large B-cell lymphoma.

Background: Despite several attempts to improve the prognosis of patients with diffuse large B-cell lymphoma (DLBCL), the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) regimen remains the standard of care in previously untreated DLBCL. A randomized phase II/III study (JCOG0601) was performed to investigate the efficacy of dose-dense weekly rituximab combined with standard CHOP (RW-CHOP). Herein, we report the final results of JCOG0601 as a post hoc assessment after an 8-year follow-up.

Methods: Patients aged 20-79 years with previously untreated DLBCL (stages I-IV, performance status 0-2) were randomized to either standard R-CHOP or RW-CHOP.

Results: Between December 2007 and December 2014, 421 patients were randomly assigned to R-CHOP (n = 213) or RW-CHOP (n = 208). With a median follow-up of 9.6 years, no meaningful differences were found in progression-free survival (PFS) and overall survival (OS) [hazard ratio (HR) in PFS, 0.94; 95% confidence interval (CI), 0.67-1.32; HR in OS, 0.94; 95% CI, 0.63-1.41]. The median PFS and OS were not estimable in both arms. Twenty-one (5.0%) cases of grade ≥ 3 cardiac toxicity were observed. The cumulative incidence rates of secondary malignancy were 14.6% and 16.8% in the R-CHOP and RW-CHOP arms, respectively. The median time from study enrollment to the onset of secondary malignancy was 4.5 years, and the incidence was time-dependent. No unexpected adverse events, including opportunistic infections, occurred.

Conclusion: These final follow-up data confirmed the nonsuperiority of RW-CHOP in terms of PFS and OS. Standard R-CHOP remains the standard of care for untreated DLBCL.