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

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

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.

Publication types

  • Clinical Trial, Phase III
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers
  • Chromosome Aberrations*
  • CpG Islands
  • Cyclophosphamide / administration & dosage
  • DNA Methylation
  • DNA Mutational Analysis
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoglobulin Heavy Chains / genetics
  • In Situ Hybridization, Fluorescence
  • Kaplan-Meier Estimate
  • Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / mortality
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Mutation
  • Prognosis
  • Treatment Outcome
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives*
  • Vidarabine / therapeutic use
  • ZAP-70 Protein-Tyrosine Kinase / genetics

Substances

  • Biomarkers
  • Immunoglobulin Heavy Chains
  • Cyclophosphamide
  • ZAP-70 Protein-Tyrosine Kinase
  • Vidarabine
  • fludarabine

Associated data

  • ClinicalTrials.gov/NCT00003764

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