Survival Impact of Rituximab Combined to ACVBP (R-ACVBP) in 209 Poor Risk Diffuse Large B-Cell Lymphoma (DLBCL) Patients Treated with Upfront High-Dose Consolidative Autotransplantation (HDC) : A GELA Phase II Study

Rituximab (R) combined with CHOP improves complete remission rate and PFS, OS in DLBCL pts. More intensive regimen followed by HDC have been used in patients < 60y with 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 study was to see if 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) translates into an improvement of response rate and also PFS, OS, EFS in pts under 60y with DLBCL and aaIPI 2 or 3. Four cycles of R-ACVBP were delivered every 15 days supported by G CSF. Responding pts received a consolidative BEAM and peripheral blood stem cell rescue. From 01/2004 to 12/2005, 209 DLCBL pts were enrolled. Median age was 49 years (range: 18–60), 22 % with aa-IPI 3, 19 % with bone marrow involvement, 93% with LDH> 1N and 54 % with extranodal sites > 1. Based on International Workshop Criteria, CR+CRu rate after induction treatment was 61%, PR rate 24%, stable disease 2% and progressive disease 1% heading an overall response rate of 84% (176pts). Deaths occurred in 4% of the pts. Hematological 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 18 pts (10%), Consequently 157 pts were responders and had successful mobilization. Among responding pts, 155 pts received HDC, representing 75% of the whole population. Four patients died without progression during the HDC procedure. At the end of treatment, the overall response rate was 81% with 150 pts (72%) considered in complete remission, 9% in PR and 4% progressed. With a median follow-up of 27 months, using the updated IWC 2007, three-year PFS was 76% (CI 69–81%), and 85% for pts submitted to HDC; OS was 81% (CI 75–86%) and 90% for pts submitted to HDC, finally EFS was 60% (CI 53–66%), and 83% for pts submitted to HDC. For pts with IPI 2 or 3, 3 y PFS were 84%–92% and OS 89%–95% respectively without significant difference. There was no significant difference between pts in CR or PR before transplant. No other prognostic factors could be isolated in multivariate analysis. We conclude that with R-ACVBP induction regimen, 75% of the patients could received HDC. There is an increase of complete remission rate after HDC according the criteria used. An impressive PFS of 76% and OS 81% were observed even in patients with 3 adverse factors. Comparison with previous study without rituximab in induction suggests a major improvement which needs confirmatory prospective randomized study.