Rituximab (R) in Combination with Fludarabine (F) and Cyclophosphamide (C) in Relapsed Follicular Lymphoma (FL) Patients (pts).Final Results of FC + R Phase II Trial by the GISL.

Fifty-four Pts entered this trial between January 2000 and December 2002. Eligible Pts had histologic documentation of CD 20⁺ relapsed FL, according to the revised European/American Lymphoma classification, that required treatment, measurable lesion, and an ECOG performance status of 0 or 1. Pts were further required to be aged 18–70 years, and to have undergone < 3 previous lines of chemotherapy. Pts received FC + R chemoimmunotherapy consisting of F 25 mg/m² and C 300 mg/m²/day for 3 consecutive days every 3 weeks for 4 cycles. R 375 mg/m² I.V. infusion was administered starting 2 weeks following the first FC course and then on day 1 of each cycle thereafter. Clinical response were defined according to the International Working Group recommendations. BCL 2 analysis was performed by PCR assay. DR, TTP and OS were analyzed by Kaplan-Meier method. Cox analysis was used to analyse the association of baseline prognostic factors with response to treatment, DR,TTP and OS. The overall response rate for all 54 Pts by ITT analysis was 90%; forty Pts (74%), obtained complete responses. Progression occurred in 3 Pts ( 6% ) and 2 Pts dropped out of the trial: 1 for toxicity and 1 refused to start with therapy. A univariate analysis of baseline prognostic factors demonstrated that none of these factors predicted for response to treatment. There were 29 Pts out of 45 tested, positive for BCL 2 before therapy. Among these, 22 Pts were evaluated after treatment and 19 ( 86%) converted to BCL negativity. At last follow up (FU), 40 Pts were alive, 31 with ongoing response and 9 with progressive disease. The median DR, TTP and OS have not been reached after a median FU time of 45 months ( range, 1 to 74 months ). The median DR in the 49 Pts who have reached CR or PR was 35 months ( range, 6 to 70 months). None of the baseline prognostic characteristics was significantly related to DR. The median TTP in all 54 Pts, was 36 months ( range, 1 to 74 months ).BCL2 positivity and < 2 previous treatments were related with better TTP (p<0.05 ) OS rate at 4 years was 75%. Toxicity was evaluable in 52 Pts. The most common severe side effects were hematologic, and included 21 cases of neutropenia, 3 cases of thrombocytopenia and 2 cases of anemia. Infectious complications manifested in 3 Pts and 1 died for pneumonitis. Treatment delays of 1–3 weeks was necessary in 12 patients. The results of our trial have demonstrated that FC+R chemoimmunotherapy is active and relatively well tolerated. The OR rate of 90%, associated with an excellent molecular remission rate, and the mean DR of 35 months compares favourably with the results obtained in other trials in similar subset of patients and supports the use of an FC+R arm in future controlled trials.