To the editor:

Chemoimmunotherapy with fludarabine (F), cyclophosphamide (C), and rituximab (R) is currently considered the gold standard first-line therapy for chronic lymphocytic leukemia (CLL).1  In an attempt to reduce the neutropenia and maintain the high response rate of standard-dose FCR, we conducted a prospective phase 2 clinical trial in untreated CLL patients using lower doses of FC and higher dose of R followed by R maintenance until progression or up to 2 years (FCR-Lite). Details of the study were previously described.2  Between June 2004 and November 2008, 65 CLL patients (median age 58 years, range 36-85 years, Rai stage I-II: 80%, Rai stage III-IV: 20%) were treated with FCR-Lite. Patients were evaluated for response using the 2008 International Workshop on CLL criteria.3  Of the 63 evaluable patients, 46 (73%) achieved complete response (CR), 2 (3%) achieved nodular partial remission (nPR), 11 (17%) achieved partial remission (PR), and 4 (6%) did not respond. Among the 50 patients with Rai stage I-II there were 38 (76%) CRs and 10 (20%) PRs and among the 13 patients with Rai stage III-IV there were 8 (62%) CRs and 3 (23%) PRs. For patients < 60 years there were 35 (81%) CRs and 5 (12%) PRs, for patients between 60-69 years there were 6 (55%) CRs and 4 (36%) PRs, and for patients ≥ 70 years there were 5 (56%) CRs and 4 (44%) PRs. For the 40 patients with normal cytogenetics, del13q or +12 there were 31 (78%) CRs, 7 (17%) PRs, and 2 (5%) NRs. Eight of 9 (89%) patients with del11q had a CR and 1 (11%) had a PR. Three of 3 patients with del17p had PRs.

The median overall survival has not been reached and the median progression-free survival was 5.8 years and the 3- and 5-year progression-free survival probability is shown in Table 1. This compares favorably with the MD Anderson Cancer Center (MDACC) phase 2 FCR trial where the 6-year actuarial OS and failure-free survival were 77% and 51%, respectively, as well as the FCR arm of the German CLL Study Group GCLLSG) where the PFS was 4.4 years.4-6 

Table 1

One-, 3-, and 5-year survival probabilities

YearOverall survival probability, % (95% confidence limits)Progression-free survival probability, % (95% confidence limits)
96.9 (88.3%, 99.2%) 93.2 (82.9%, 97.4%) 
87.6 (76.7%, 93.6%) 84.6 (72.6%, 91.7%) 
85.5 (73.9%, 92.2%) 66.9 (49.7%, 79.3%) 
YearOverall survival probability, % (95% confidence limits)Progression-free survival probability, % (95% confidence limits)
96.9 (88.3%, 99.2%) 93.2 (82.9%, 97.4%) 
87.6 (76.7%, 93.6%) 84.6 (72.6%, 91.7%) 
85.5 (73.9%, 92.2%) 66.9 (49.7%, 79.3%) 

Fifty-five patients (85%) completed all 6 courses of FCR-Lite with dose reduction in 2% of total cycles. Grade 3-4 neutropenia occurred in 11% of total cycles of FCR-Lite and grade 3-4 infections were seen in 6% of patients. Three patients developed myelodysplastic syndromes and 2 patients developed B-cell lymphomas after FCR-Lite therapy.

In summary, the FCR-Lite regimen represents an active frontline treatment with excellent responses and duration of response with a favorable toxicity profile. Interpretation of these data and comparisons with the MDACC and GCLLSG trials should be viewed in light of the relatively low numbers of patients, relatively early Rai stages of the patients, use of prophylactic growth factors, and maintenance rituximab in the FCR-Lite trial. Further studies with FCR-Lite will include combination therapies with promising new agents.

Authorship

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Correspondence: Kenneth A. Foon, Celgene Corporation, 86 Morris Ave, Summit, NJ 07901; e-mail: kfoon@celgene.com.

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