Rituximab Combined to ACVBP (R-ACVBP) Supported by Pegfilgrastim as a New Inductive Treatment Followed by High-Dose Consolidative Autotransplantation (HDC) for Poor Risk Diffuse Large B-Cell Lymphoma (DLBCL) in First-Line. Results of LNH 03–39B. A GELA Study

ACVBP dose-intense induction regimen followed by HDC provides a better event-free survival and overall survival (OS) as compared to a conventional consolidative treatment in responding patients (pts) with aggressive lymphoma presenting with 2 or 3 factors of the age-adjusted International Prognostic Index (aa-IPI). However, complete response rate (CRR = CR+CRu) after ACVBP is not superior to 65%. Besides, it is established that Rituximab (R) combined with CHOP improves CRR and OS. Several controlled studies have demonstrated that a single dose of pegfilgrastim provides similar neutrophil recovery than filgrastim after chemotherapy in cancer patients. The main objective of this study was to evaluate the efficacy of a single dose of pegfilgrastim (6 mg) at d3 of the 4 cycles of R-ACVBP inductive regimen (rituximab 375 mg/m2 d1,doxorubicin 75 mg/m2 d1, cyclophosphamide 1,200 mg/m2 d1, vindesine 2 mg/m2, bleomycin 10 mg d1 and d5 and prednisone 60 mg/m2 d1-d5) delivered every 15 days in order to maintain an optimal combined dose intensity (CDI). CDI was defined as the minimum received dose intensities of doxorubicin and cyclophosphamide by each patient. Secondary objectives were to investigate if R combined to ACVBP translates into an improvement of CRR and progression free survival (PFS). The number of leukaphereses and CD34+ cells collected in responding pts were also analyzed. Responding pts received HDC with BEAM followed by stem cell rescue. From 01/2004 to 12/2005, 60 pts were enrolled: median age was 50 y (range: 21–60), 80% with aaIPI 2 and 20% with aa-IPI 3. The mean CDI was 89 (95% CI: 86–93), greater than theoretical cut-off of 85% (p=0.0017). After induction, 63% of pts achieved CR/CRu, 25% were in PR; 2 pts died during the induction phase. At least one episode of grade 3–4 neutropenia was observed in 98% of pts, 67% experienced grade 3–4 anemia, 38% thrombocytopenia and 73% febrile neutropenia. More than 2.106 CD34+ cells/kg were collected in 80% of the pts after the 3rd and/or 4th R-ACVBP while a collection failure was observed in 11 pts (20%), 7 of them being further collected with filgrastim. The median number of leukaphereses was 2. Among the 56 responding pts, 48 received HDC. With a median follow-up of 2 years, 2-year PFS was 71% (95% CI:61–84), and OS was 91% (95% CI:74–97). We conclude that CDI is satisfactory with pegfilgrastim support. R-ACVBP dose-intense induction regimen is feasible and safe on such high-risk pts but does not increase the complete response rate. However, PFS and OS seem encouraging; a longer follow-up is needed to see whether the addition of rituximab definitely contributes to decrease the relapse rate.