Improved outcome of elderly patients with poor-prognosis diffuse large B-cell lymphoma (DLBCL) after dose-dense rituximab: Results of the DENSE-R-CHOP-14 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL)

Abstract

8508 Background: While 6 to 8 cycles of CHOP in combination with rituximab (R) are widely accepted as standard regimen of care for aggressive lymphomas, the optimal dose and number of R application have not been determined to date. In a previous pharmacokinetic study we had shown that the concomitant application of CHOP and R does not achieve a plateau of R trough levels until cycle 5 (Reiser, Blood 108, 778a, 2006). In order to achieve high R levels early, we increased the number of R applications. Methods: 100 elderly pat. with aggressive CD20+ B-cell lymphoma received 6 cycles of biweekly CHOP-14 combined with 12x R (375 mg/m2) on days 0,1,4,8,15,22,29,43,57,71,85, and 99. Radiotherapy was planned to sites of initial bulk and/or extranodal involvement. The primary endpoint was event-free survival (EFS). 306 pat. treated within the RICOVER-60 trial (Pfreundschuh et al., Blood 64a, 2006) with 6xCHOP-14 and 8 applications of R served as control. Results: 97/100 pat. are evaluable for response. Plateau trough serum levels were achieved by day 1 of the first chemotherapy cycle and higher R levels were maintained throughout the treatment compared to 8 bi-weekly applications. Because 3 therapy-associated deaths were observed among the first 20 pat. treated, prophylaxis with levofloxacin, acyclovir and cotrimoxazol became mandatory for the following pat.. Despite a less favorable study population DENSE-R-CHOP-14 resulted in a somewhat higher CR (83% vs. 78%) and lower progression under therapy rate (5% vs. 7%) rate, but event free and overall survival were not different compared to 8 biweekly applications of R. However, a subgroup analysis of pat. according to IPI risk group showed that DENSER-R-CHOP-14 resulted in a higher complete response rate of pat. with poor-prognosis (IPI:3–5) disease (81% vs. 68%) and in a better 1-year event-free survival rate (74% vs. 65%) of these pat.. Conclusion: Densification of R results in higher serum levels and in higher complete remission and event-free survival rates in elderly pat. with poor-prognosis DLBCL. An update of the results of the completed trial with 125 pat. will be presented. Supported by Dt. Krebshilfe and Roche. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech, Lilly, Roche Genentech, Lilly, Roche Roche