One third of patients with newly diagnosed, advanced chronic lymphocytic leukemia (CLL) who received the combination of bendamustine and rituximab achieved a complete response, according to researchers from the German CLL Study Group.
Another 56% of the patients treated with this combination had partial responses, said principal investigator Kirsten Fischer, MD, Center of Integrated Oncology, University of Cologne, Germany, at the annual meeting and exposition of the American Society of Hematology.
Bendamustine had already been shown to have considerable activity as monotherapy in CLL and many other lymphoid cancers, as well as in combination with rituximab in patients with relapsed or refractory CLL.
This new study examined bendamustine in combination with rituximab as first-line therapy in 117 patients, 48% of whom had Binet stage C disease and 41% of whom had Binet stage B.
Rituximab was given as four 6-week cycles with two doses of bendamustine in each cycle. Some 72% of patients in the study were treated with all six cycles of therapy.
The median observation time was 15.4 months, and the overall response rate was 90.9%. A complete response was observed in 32.7% and a partial response in 55.5%. All other patients (9.1%) had stable disease, and none of the patients had progressive disease. With up to 26 months of follow-up, 75.8% of the patients were still in remission, and median progression-free survival has not been reached.
Objective response rates of approximately 90% were achieved among the different genetic subgroups, except for del(17p), a high-risk subgroup in which the partial response rate was 42.9%.
Complete responses occurred most often in patients with unmutated immunoglobulin variable region heavy chain. The overall response rate in this group was 88.9%.
Hematologic toxicities were grade 3/4 anemia in 4.9%, grade 3/4 leukopenia in 14.6%, grade 3/4 neutropenia and throm bocytopenia in 6.5% and 6.1% of all given courses, respectively. Twenty-nine episodes of common toxicity criteria grade ≥3 infections were documented (5.1% of all courses).
There were two treatment-related deaths during the study: one fatal pneumonia and one case of sepsis related to neutropenia.
Based on these encouraging data, the group is now conducting a phase 3 trial in which the efficacy of bendamustine/rituximab is being compared with fludarabine-based immunochemotherapy in the first-line treatment of CLL, said Fischer.