Abstract
Introduction Standard FCR therapy in untreated CLL patients (F-25 mg/m2 d1–3 q 4wk; C-250 mg/m2 d 1–3 q 4wk; R-500 mg/m2 d1 q 4wk for 6 cycles) was reported to have complete remissions (CR) of 70% and overall responses (OR) of 95% (
J Clin Oncol 2005;23:4079
). The major toxicity was grade 3/4 neutropenia during 52% of treatment courses. One approach to decrease neutropenia without compromising efficacy could be by reducing the doses of F and C and increasing the dose of R. Methods We conducted a phase II study for previously untreated advanced CLL patients treated with FCR-Lite (F-20mg/m2 d1–3 q 4 wk; C-150 mg/m2 d1–3 q 4 wk; R-500mg/m2 d1 and d14 q 4wks; maintenance R-500 mg/m2 ×1 q 3 months until progression). A Simon two-stage design was used where 15 patients were accrued in the first stage and because of acceptable toxicity and response rate in stage I an additional 35 patients were treated. The primary endpoint was response rate. Results A total of 50 patients were entered into this study and 42 are currently evaluable. There were 29 male and 13 female patients with an age range of 36–85 years (median 58) treated with a total of 236 courses of FCR-Lite. All 42 patients were evaluable for toxicity. Grade 3/4 neutropenia occurred during 29 (12%) courses with two episodes of neutropenic fever. One patient had cellulitis, another had pneumonia (not neutropenic). Grade 3/4 thrombocytopenia occurred during 7 (3%) courses and grade III/IV anemia during 6 (2.5%) courses. Among the 40 evaluable patients for response, the CR rate was 85%, PR rate was 15% with an OR rate of 100%. All of the CR patients were tested by flow cytometry and had <1% CD5+/CD19+ cells in their bone marrow after therapy. One patient with potential CR was excluded due to the absence of follow up bone marrow biopsy. Minimal residual disease (MRD) was tested by four color flow cytometry (sensitivity 0.01%) in 8 patients with CR (Genzyme Genetics Corp.). Seven had no evidence of MRD at 7, 8, 8, 14, 22, 25 and 30 months respectively, post CR, and one patient had 0.03% and 0.06% when tested at 12 and 18 months post CR respectively. Conclusions Our results in 42 patients suggest FCR-Lite is highly effective with considerably less grade 3/4 neutropenia than standard FCR. Complete responders had no detectable CD5+/CD19+ cells in their bone marrow following FCR-Lite. MRD testing is currently underway for all patients.Author notes
Disclosure:Research Funding: This study is supported by Genentech, Inc. Membership Information: Dr. Ken Foon is on Genentech’s Speaker’s Bureau.
2007, The American Society of Hematology
2007
