Fludarabine, cyclophosphamide and rituximab for chronic lymphocytic leukemia: no country for old men?

The combination of fludarabine, cyclophosphamide and rituximab is regarded as the gold-standard treatment for chronic lymphocytic leukemia in many parts of the world, although rituximab has not yet been licensed for this use. To date, no randomized, controlled trials have been fully published that demonstrate the superiority of this regimen over other treatments. The results of an open-label, phase II trial with long-term follow-up data on 300 patients with chronic lymphocytic leukemia treated with this regimen are discussed here. Although this study reported impressive efficacy, information on modern prognostic markers such as immunoglobulin gene mutational status and chromosomal deletions was absent, and so it is impossible to say whether the most challenging cases, as identified by these markers, were included in the trial. The most important toxicity was prolonged cytopenia, which occurred both at the end of treatment and later after bone-marrow recovery. At least half of patients with chronic lymphocytic leukemia are over 70 years of age and this regimen might be too toxic for such individuals.