Seventy percent of complete responders remain in continuous remission: Five-year follow-up of 300 patients treated with fludarabine, cyclophosphamide, and rituximab (FCR) as initial therapy of CLL

Abstract

7008 Background: The early results of 224 CLL patients receiving the FCR regimen were previously reported (JCO 23:4079). Mature follow-up data (median 62 months for survivors) is now available for the complete cohort of 300 patients. Methods: Eligible patients were =16 years old with previously untreated CLL requiring therapy. Median age was 57 years (31%=60 years, 14% =70 years), and 61% & 36% were in modified Rai intermediate & high risk categories respectively. Prognostic factors: B2m >2x normal 42% (n=295), CD38 positive 28% (n=253), abnormal metaphase cytogenetics 29% (n=221), IgVH unmutated 66% (n=94), ZAP-70 positive 49% (n=88). The planned six cycles of therapy were completed in 74% patients. Results: Responses were: 72% CR, 11% nodular PR (PRn) & 12% PR. On multivariate analysis, CR rates were inferior in patients with B2m >2N (p=0.001) and white cell count >150 × 109/L (p=0.01). Rai stage, CD38 positivity, IGVH mutational status and ZAP-70 positivity were not associated with inferior CR. Median Times to Progression (TTP) were 80 months for CR (n=216), 80 months for PRn (n=32) & 27 months for PR (n=36), with 77%, 65% and 28% projected to be progression-free at five years; projected 5 yr survival were 90%, 81% and 37% respectively. Restricting the analysis to 190 patients with at least five years followup, actual 5 yr TTP and 5yr survival were 70% & 88% respectively in complete responders. Five cases of Richter transformation and eight cases of MDS/AML occurred during remission, with projected 5 yr risk of 2% & 3% respectively. When compared with a historical cohort of patients receiving fludarabine (n=190) or fludarabine and cyclophosphamide/mitoxantrone (n=140) in multivariate analysis, FCR was independently associated with superior TTP (p<0.001) and survival (p<0.001). Conclusion: FCR is the most effective CLL frontline regimen reported to date. 70% of complete responders remain progression-free at five years. No significant financial relationships to disclose.