title: Chemoimmunotherapy with fludarabine and rituximab produces extended overall survival and progression-free survival in chronic lymphocytic leukemia: long-term follow-up of CALGB study 9712.
abstract: OBJECTIVE
  The addition of rituximab to fludarabine-based regimens in chronic lymphocytic leukemia (CLL) has been shown to produce high response rates with extended remissions. The long-term follow-up of these regimens with respect to progression, survival, risk of secondary leukemia, and impact of genomic risk factors has been limited.
  
  
  METHODS
  We report the long-term follow-up of the chemoimmunotherapy trial CALGB 9712 from the Cancer and Leukemia Group B, for which treatment regimen was previously reported, to examine end points of progression-free survival (PFS), overall survival (OS), impact of genomic features, and risk of therapy-related myeloid neoplasm (t-MN).
  
  
  RESULTS
  A total of 104 patients were enrolled on this study and now have a median follow-up of 117 months (range, 66 to 131 months). The median OS was 85 months, and 71% of patients were alive at 5 years. The median PFS was 42 months, and 27% were progression free at 5 years. An estimated 13% remained free of progression at almost 10 years of follow-up. Multivariable models of PFS and OS showed that immunoglobulin heavy chain variable region mutational status was significant for both, whereas cytogenetic abnormalities were significant only for OS. No patient developed t-MN before relapse.
  
  
  CONCLUSIONS
  Long-term follow-up of CALGB 9712 demonstrates extended OS and PFS with fludarabine plus rituximab. Patients treated with fludarabine plus rituximab administered concurrently or sequentially have a low risk of t-MN. These long-term data support fludarabine plus rituximab as one acceptable first-line treatment for symptomatic patients with CLL.
authors.affiliation: The Ohio State University, 320 West 10 Ave, Columbus, OH 43210, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Woyach
authors.forename: Amy S
authors.initials: AS
authors.lastname: Ruppert
authors.forename: Nyla A
authors.initials: NA
authors.lastname: Heerema
authors.forename: Bercedis L
authors.initials: BL
authors.lastname: Peterson
authors.forename: John G
authors.initials: JG
authors.lastname: Gribben
authors.forename: Vicki A
authors.initials: VA
authors.lastname: Morrison
authors.forename: Kanti R
authors.initials: KR
authors.lastname: Rai
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D020732:Cytogenetic Analysis; D018572:Disease-Free Survival; D050438:Genes, Immunoglobulin Heavy Chain; D006801:Humans; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000401:mortality; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced; D008131:London; D009154:Mutation; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D000069283:Rituximab; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D014740:Vidarabine; C024352:fludarabine