Six vs. Eight Cycles of Bi-Weekly CHOP-14 with or without Rituximab for Elderly Patients with Diffuse Large B-Cell Lymphoma (DLBCL): Results of the Completed RICOVER-60 Trial of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL).

Interval reduction from 3 (CHOP-21) to 2 weeks (CHOP-14; Pfreundschuh et al., Blood, 2004 ) and the addition of rituximab to CHOP-21 (R-CHOP-21; Coiffier et al., NEJM, 2002 ) improved outcome in elderly patients with DLBCL to a similar extent compared to CHOP-21. In the RICOVER-60 trial, elderly patients (61–80 years) were randomized to receive 6 or 8 cycles of CHOP-14 with or without rituximab given on days 1, 15, 29, 43, 57, 71, 85, and 99. Radiotherapy was planned to sites of initial bulk and/or extranodal involvement. Between 07/2000 and 06/2005, 1222 patients with CD20 + DLBCL and informed consent were recruited and evaluable (median age 68 years; IPI=1: 30%, IPI=2: 28%; IPI=3: 26%; IPI=4,5: 16%). The primary endpoint was event-free survival (EFS) with events defined as additional therapy, failure to achieve complete remission, progressive disease, relapse, or death. As by intention to treat, the 3-year EFS rate was 47% after 6×CHOP-14 (n=307), 53% after 8×CHOP-14 (n=305), 66% after 6×R-CHOP-14 (n=306), and 63% after 8×R-CHOP-14 (n=304). Regarding time-to-event data, we found a relevant interaction term (RR 1.4, p=0.068) between treatment contrasts and performd according to the protocol single-arm comparisons using 6×CHOP-14 without rituximab as the reference arm instead of a 2×2 factorial analysis. The p-values for the univariate log-rank tests of the improvement in EFS over 6×CHOP-14 were p=0.036 for 8×CHOP-14, and p + DLBCL. 6×R-CHOP-14 should be considered as reference standard in future trials for elderly patients with DLBCL.