Rituximab Combined to ACVBP (R-ACVBP) as a New Inductive Treatment Followed by High-Dose Consolidative Autotransplantation (HDC) for Poor Risk Diffuse Large B-Cell Lymphoma (DLBCL) in First-Line. Preliminary Results on 119 Patients of a GELA Phase II Study.

ACVBP induction regimen followed by HDC provides a better event-free survival (EFS) and overall survival (OS) as compared to a conventional consolidative treatment in patients (pts) with aggressive non Hodgkin’s lymphoma presenting with 2 or 3 adverse age-adjusted International-Prognostic-Index (aa-IPI) who first reached complete remission. However, complete response rate (CR +CRu) after ACVBP is not superior to 65% (ASH 2005, 677a). Besides, it is established that Rituximab (R) combined with CHOP improves complete remission rate and OS in elderly pts.

The objective of the study was to see if combining R (375 mg/m2) to ACVBP (Doxorubicin 75 mg/m2 d1, Cyclophosphamide 1,200 mg/m2 d1, Vindesine 2 mg/m2 and Bleomycin 10 mg d1 and d5, prednisone 60 mg/m2 d1-d5) translates into an improvement of response rate and also EFS in pts under 60y with DLBCL and aaIPI 2 or 3. Four cycles of R-ACVBP were delivered every 15 days supported by filgrastim 5 μg/kg (d6 to d13) or pegfilgrastim (6 mg at day 3). Responding pts received a consolidative BEAM and peripheral blood stem cell rescue.

From 01/2004 to 12/2005, 119 DLCBL pts were enrolled. Median age was 49 years (range: 19–60), 18% with aa-IPI 3, 22% with bone marrow involvement, 96% with LDH> 1N and 88% with extranodal sites>1. 59 pts received filgrastim and 60 pegfilgrastim. Based on International Workshop Criteria, CR+CRu rate after induction treatment was 63%, PR rate 25%, stable disease 3% and progressive disease 1%. Deaths without progression occurred in 3% of the pts, and 6% of them could not be assessed (treatment was stopped because of toxic effects or major protocol violation). Hematologic toxicity was similar to that observed in previous GELA trials using ACVBP. Collection failure after the 3rd and/or 4th R-ACVBP cycle was observed in 15 pts (13%), 4 receiving filgrastim and 11 pegfilgrastim (7 of them being further collected with filgrastim). Among the 105 responding pts, 90 received HDC, 15 pts did not (physician’s decision for 4 PET-positive pts after 4 R-ACVBP, 8 collection failures, 2 pts because of a poor performance status after induction phase and one due to sudden death). Three patients died without progression during the HDC procedure. At the end of treatment, 81 pts (68%) were considered in complete remission, 14% in PR and 6% progressed. With a median follow-up of 15 months, two-year EFS was 72% ( CI 62–68%), OS was 79% ( CI 69–86%).

We conclude that R-ACVBP induction regimen is feasible and safe on such high risk pts but it does not increase the CR rate. EFS seems encouraging; a longer follow-up is needed to see whether the addition of rituximab contributes to decrease the incidence of relapse.