Updated Results of the FOLL05 Phase III Trial from the Fondazione Italiana Linfomi Comparing R-CVP, R-CHOP, and R-FM in Patients with Advanced Follicular Lymphoma.

8530 Background: The final results of FOLL05 for the initial therapy of advanced stage follicular lymphoma (FL) were recently reported with a median follow–up of 34 months. This trial showed that R–CHOP and R–FM were superior to R–CVP in terms of 3–year time to treatment failure (TTF), the primary study endpoint, and that R–CHOP had a better risk/benefit ratio compared with R–FM. Here, we present the 5–year follow–up analysis of progression free survival (PFS) of the 504 patients included in the study. Methods: Patients were 18–75 year old, with untreated stage II–IV FL, ECOG performance status of 0–2, and active disease according to the Italian Society of Hematology guidelines. They were randomly assigned to receive 8 doses of rituximab associated to 8 cycles of CVP, or 6 cycles of CHOP or FM. Maintenance was not admitted. Results: The median follow–up was 56 months (range 1–90). The overall 5–year TTF was 52% (95%CI, 47–56%). R–CHOP and R–FM had a better TTF compared to R–CVP (56% and 56% vs 43% at 5–years; p= 0.007 and p=0.017, respectively). Regarding PFS a total of 215 events were recorded, thus determining a 5–year PFS of 56% (95%CI, 52-61%). Compared to initial report 31 additional events for PFS were observed and were mainly represented by lymphoma relapses (80%). Better PFS rates were observed for R–CHOP and R–FM compared to R–CVP (62% and 60% vs 47% at 5–years). After adjustment by FLIPI, and using R–CVP as reference, HRs for PFS were 0.66 for R–CHOP (95%CI, 0.47–0.92; p=0.013), and 0.71 for R–FM (95%CI, 0.52–0.98; p=0.035); the HR between R–FM and R–CHOP was 1.08 (95%CI, 0.76–1.52; p=0.677). Considering additional events reported during the follow–up, 27 second malignancies were recorded in all treatment arms: four in R–CVP, 9 in R–CHOP and 14 in R–FM (p=0.062; R–CVP vs R–CHOP, p=0.169; R–CVP vs R–FM, p=0.018). Finally with 47 recorded deaths the 5–year overall survival rate was 91% (95%CI, 87–93%). Conclusions: The 5–year update of the FOLL05 study, with mature data on PFS, confirms that R–CHOP has the best efficacy profile compared to R–CVP and R–FM for the initial treatment of patients with advanced FL. Clinical trial information: NCT00774826.