First-line rituximab (R) high-dose therapy (R-HDT) versus R-CHOP14 for young adults with diffuse large B-cell lymphoma: Preliminary results of the GOELAMS 075 prospective multicenter randomized trial.

8003 Background: We have shown that first-line HDT leads to an improved EFS and OS over CHOP in adults with aggressive NHL (NEJM 2004) and that adding R to the HDT was feasible and might improve the results (BBMT 2010). We present the preliminary analysis of a multicenter RCT comparing R-CHOP14 to R-HDT in adults with DLBCL (clinical trial.gov: NCT 00561379). Methods: Pts 18 to 60 y.o. CD20 + DLBCL AA stage 1-2 with bulk ≥ 7 cm or 3 -4 were rdz at dg (stratified on aaIPI) between R-CHOP14 (8 courses if response after the first 4) and R-HDT. This consisted of 2 courses of HD CHOP-like, 15 days apart, with R (375/mg/m2) on day 1 of each, then R on d 22, harvest of G-CSF mobilized PBSC on d 28, 29, R on d 36 followed by HD methotrexate with cytarabin. For pts who achieved a response after these 3 courses, BEAM started on d 66 to 80 followed by PBSCT. In each arm, the interm response was assessed by CT Scan and PET (Cheson criteria JCO 2007). Pts not achieving a PR or a neg PET had a salvage Tx and auto PBSCT. Results: 340 pts included 01/2005 to 06/2010, 286 pts evaluable at time of abstract, 143 in each arm. Characteristics of the pts in the 2 arms are super imposable. Overall 56% bulk, 72% >2 AA stage and 58% aa IPI>1. The Rdz tx was completed in 67% in the R-CHOP arm and 53% in the R-HDT arm. The interm evaluation showed the same rate of response with CT scan (CR + CRu: 65% and 62% following 4 x R-CHOP14 and first 3 courses of R-HDT). PET remained more often pos after the first 3 courses of R-HDT (41% vs 28%; p=0.03). Of the 98 pts with pos interm PET, 84 had a salvage of which 62 underwent auto PBSCT. On ITT the ORR (CR + Cru) was 82% and 76% in the R-CHOP and R-HDT arms respectively (p=0.8). With a med FU of 25 m, the 3y OS is 83%. No difference according to the tx arm in any of the aaIPI strata. The 3y PFS and DFS are 76% and 83%, no difference according to the tx arm. The 3 y OS and DFS for pts in R-CHOP arm and in R-HDT arm acc to interm PET are shown in the table. Conclusions: R-CHOP14 is as efficient, less toxic, and spares resources as compared to this R-HDT program. Salvage based on interm PET is not harmful and provides excellent results. PET neg PET pos R-CHOP 3y OS/DFS 88% / 80% 84% / 82% R-HDT 3y OS/DFS 80% /92% 86% / 89%