Benefit of rituximab combined to ACVBP (R-ACVBP) over ACVBP in 209 poor- risk BDLC NHL patients treated with up-front consolidative autotransplantation: A GELA phase II trial (LNH 2003–3)

8507 Background: Rituximab (R) combined with CHOP improves survival in DLBCL pts. More intensive regimen followed by auto transplantation have been used in patients < 60y with 2–3 adverse age-adjusted International-Prognostic-Index (aa-IPI) factors, providing a 5y OS of 65% (CI 60–68%), (Haioun LNH 98–3B, ASCO 2007). The objective of the present study was to assess whether or not combining R (375 mg/m2) to the dose intense 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) also translates into a survival benefit. Methods: From 01/2004 to 12/2005, 209 DLCBL pts < 60y with DLBCL and aaIPI 2 or 3 received 4 cycles of R-ACVBP every 15 days. CR and PR pts received a consolidative BEAM and peripheral blood stem cell rescue (LNH2003–3 trial, # NCT00144807 ). Median age was 49 years, 22 % of patients presented with aa-IPI 3, 58% with IPI 3–5 (93% with elevated LDH and 54 % with extranodal sites >1). CR rate after induction was 61%, PR rate 24% leading to an overall response rate of 84% (176 pts). Collection failure was observed in 18 pts (10%). 155 pts received auto transplantation, representing 75% of the study population. Results: With a median follow-up of 27 months, according to the updated IWC 2007, 3y PFS and OS were estimated at 76% (CI 69–81%) and 81% (CI 75–86%), respectively. A case-controlled study was performed by matching the present R-ACVBP population with ACVBP patients selected from the LNH-98–3 trial. Patients were fully matched (1:1) on histology, aa-IPI score, gender, age and follow-up duration. 3y PFS was higher in R-ACVBP than in ACVBP patients: 75% (CI 67–81%) vs 58% (CI 50–65%), p=0.0003. 3y OS were estimated at 78% (CI 71–84%) vs 67% (CI 58–74%), p=0.05. The gain in 3y OS was significant in patients who received auto transplantation: 89% (CI 81–93%) vs 77% (CI 67–84%), p=0.02. Conclusions: These results with R-ACVBP induction and consolidative auto-transplantation suggest a major survival benefit which needs confirmatory prospective study. No significant financial relationships to disclose.