Research in context
Evidence before this study
We searched PubMed between April 1, 2007, and Jan 31, 2008 for reports with the search terms “CLL”, and “clinical trial” and “chemotherapy” and “antibody” without date or language restrictions. Publications showed promising results for chemoimmunotherapy regimens based on purine analogues with or without CD20 antibodies or with the CD52 antibody alemtuzumab. First data from the CLL8 study of the German CLL Study Group presented at the American Society of Hematology Meeting in December, 2007, showed the superiority of the fludarabine, cyclophosphamide, and rituximab regimen over chemotherapy alone. On the other hand, all purine analogue-based combinations were associated with toxic effects. First data from a phase 2 trial evaluating bendamustine and rituximab had favourable results with regard to toxic effects and good efficacy. In 2007, the National Institutes of Health registry for clinical trials listed no clinical trials with a head-to-head comparison of fludarabine, cyclophosphamide, and rituximab with bendamustine and rituximab in chronic lymphocytic leukaemia.
Added value of this study
The CLL10 study is the first trial directly comparing bendamustine-based chemoimmunotherapy with fludarabine and cyclophosphamide-based chemoimmunotherapy. The data confirm data from a meta-analysis suggesting the superiority of fludarabine and cyclophosphamide-based chemoimmunotherapy over bendamustine-based chemoimmunotherapy.
Implications of all the available evidence
In a head-to-head comparison bendamustine and rituximab is less effective than the standard therapy, but can be considered in patients older than 65 years with chronic lymphocytic leukaemia. Higher incidence of adverse events observed with fludarabine, cyclophosphamide, and rituximab in patients older than 65 years and good efficacy with bendamustine and rituximab in this group might support the use of bendamustine and rituximab in fit elderly patients. Moreover, our data show that immunosuppressive effects are long lasting with fludarabine and cyclophosphamide-based therapy. Prophylactic use of co-trimoxazole against Pneumocystis jirovecii pneumonia or virostatics against herpes virus infections in patients with previous infections should be considered in patients receiving front-line chemoimmunotherapy.