Six versus eight cycles of biweekly CHOP-14 with or without R in elderly patients (pts) with aggressive CD20⁺ B-cell lymphomas: Seven-year FU of the RICOVER-60 trial of the DSHNHL.

8029 Background: Interval reduction from 3 (CHOP-21) to 2 wks (CHOP-14) and the addition of R to CHOP-21 (R-CHOP-21) improved outcome in elderly pts with DLBCL to a similar extent compared to CHOP-21. Methods: In the RICOVER-60 trial, elderly pts.(61-80 yrs) were randomized to receive 6 or 8 cy CHOP-14 with or without 8 cy R. RX was planned to sites of initial bulk and/or extranodal inv. The primary endpoint was EFS, secondary endpoints were PFS and OS. Results:Between 07/2000 and 06/2005, 1,222 pts with CD20+ DLBCL were recruited and are evaluable (med age 68 yrs; IPI=1: 30%, IPI=2: 28%, IPI=3: 26%, IPI=4,5: 16%). There was no difference between the 4 arms with respect to long-term tox and 2nd neoplasms. As by intention to treat, the 7-yr EFS rate was 33% after 6xCHOP-14 (n=307), 40% after 8xCHOP-14 (n=305), 50% after 6xR-CHOP-14 (n=306), and 52% after 8xR-CHOP-14 (n=306). After a median obs time of 82 mo, the estimated 7-yr OS rates were 50% for 6xCHOP-14, 52% for 8xCHOP-14, 62% for 6xR-CHOP-14, and 60% for 8xR-CHOP-14. In a multivariate analysis using 6xR-CHOP-14 without R as the reference and adjusting for the stratification variables elevated LDH, stage III&IV, ECOG ps>1, bulky dis, >1 extranodal site, and age >70, both R arms had a significantly improved EFS (6xR-CHOP-14: RR=0.5, p<0.001; 8xR-CHOP-14: RR=0.5, p<0.001), PFS (6xR-CHOP-14: RR=0.5, p<0.001; 8xR-CHOP-14: RR=0.5; p<0.001) and OS (6xR-CHOP-14: RR=0.6; p<0.001; 8xR-CHOP-14: RR=0.7; p=0.004). 6xR-CHOP-14 was slightly better than 8-R-CHOP-14 with respect to all endpoints and had a significantly better OS in pts with bulky dis (p=0.005). Conclusions: In contrast to the 3-yr FU, not only 6xR-CHOP-14, but also 8xR-CHOP-14 achieved a significantly better OS compared to 6xCHOP-14 after a med obs time of 82 mo. Due to its lower tox and shorter time under CTX (6xCHOP-14: 10 wks, 8xCHOP-14: 15 wks, and 8x-CHOP-21 even 21 wks, each plus 1 d), 6xCHOP-14 in comb with 8 app of R is the preferred regimen for elderly patients with CD20+ DLBCL. The significant superiority of 6xR-CHOP-14 over 8xR-CHOP-21 in pts with bulky dis, who received RX to the resp areas, suggests that RX to bulky dis is more effective when given after 6 than after 8 cy of R-CHOP-14.