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Clinical Trial
. 2015;56(11):3031-7.
doi: 10.3109/10428194.2015.1023800. Epub 2015 Mar 30.

Cytogenetic prioritization with inclusion of molecular markers predicts outcome in previously untreated patients with chronic lymphocytic leukemia treated with fludarabine or fludarabine plus cyclophosphamide: a long-term follow-up study of the US intergroup phase III trial E2997

David M Lucas  1 , Amy S Ruppert  1 , Gerard Lozanski  1 , Gordon W Dewald  2 , Arletta Lozanski  1 , Rainer Claus  3   4 , Christoph Plass  4 , Ian W Flinn  5 , Donna S Neuberg  6 , Elisabeth M Paietta  7 , John M Bennett  8 , Diane F Jelinek  2 , John G Gribben  9 , Mohamad A Hussein  10 , Frederick R Appelbaum  11 , Richard A Larson  12 , Dennis F Moore Jr  13 , Martin S Tallman  14 , John C Byrd  1 , Michael R Grever  1
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Clinical Trial

Cytogenetic prioritization with inclusion of molecular markers predicts outcome in previously untreated patients with chronic lymphocytic leukemia treated with fludarabine or fludarabine plus cyclophosphamide: a long-term follow-up study of the US intergroup phase III trial E2997

David M Lucas et al. Leuk Lymphoma. 2015.

Abstract

Fludarabine (F) and cyclophosphamide (C) remain backbones of up-front chemotherapy regimens for chronic lymphocytic leukemia (CLL). We report long-term follow-up of a randomized F vs. FC trial in untreated CLL (#) . With median follow-up of 88 months, estimated median progression-free survival (PFS) was 19.3 vs. 48.1 months for F (n = 109) and FC (n = 118), respectively (p < 0.0001), and median overall survival (OS) was 88.0 vs. 79.1 months (p = 0.96). In multivariable analyses, variables associated with inferior PFS and OS respectively were age (p = 0.002, p < 0.001), Rai stage (p = 0.006, p = 0.02) and sex (p = 0.03, PFS only). Del(17)(p13.1) predicted shorter PFS and OS (p < 0.0001 for each), as did del(11q)(22.3) (p < 0.0001, p = 0.005, respectively), trisomy 12 with mutated Notch1 (p = 0.003, p = 0.03, respectively) and unmutated IGHV (p = 0.009, p = 0.002, respectively), all relative to patients without these features. These data confirm results from shorter follow-up and further justify targeted therapies for CLL.

Trial registration: ClinicalTrials.gov NCT00003764.

Keywords: Fludarabine; chemotherapy; chronic lymphocytic leukemia; cyclophosphamide.

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Conflict of interest statement

CONFLICT OF INTEREST STATEMENT: No authors have conflicts of interest with this work.

Figures

Figure 1
Figure 1. Kaplan-Meier curves by treatment arm
A) Progression-free survival; B) Overall survival.
Figure 2
Figure 2. Kaplan-Meier curves by cytogenetic/molecular classification
A) Progression-free survival; B) Overall survival.
See this image and copyright information in PMC

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