title: Early Relapse of Follicular Lymphoma After Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Defines Patients at High Risk for Death: An Analysis From the National LymphoCare Study.
abstract: OBJECTIVE
  Twenty percent of patients with follicular lymphoma (FL) experience progression of disease (POD) within 2 years of initial chemoimmunotherapy. We analyzed data from the National LymphoCare Study to identify whether prognostic FL factors are associated with early POD and whether patients with early POD are at high risk for death.
  
  
  METHODS
  In total, 588 patients with stage 2 to 4 FL received first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Two groups were defined: patients with early POD 2 years or less after diagnosis and those without POD within 2 years, the reference group. An independent validation set, 147 patients with FL who received first-line R-CHOP, was analyzed for reproducibility.
  
  
  RESULTS
  Of 588 patients, 19% (n = 110) had early POD, 71% (n = 420) were in the reference group, 8% (n = 46) were lost to follow-up, and 2% (n = 12) died without POD less than 2 years after diagnosis. Five-year overall survival was lower in the early-POD group than in the reference group (50% v 90%). This trend was maintained after we adjusted for FL International Prognostic Index (hazard ratio, 6.44; 95% CI, 4.33 to 9.58). Results were similar for the validation set (FL International Prognostic Index-adjusted hazard ratio, 19.8).
  
  
  CONCLUSIONS
  In patients with FL who received first-line R-CHOP, POD within 2 years after diagnosis was associated with poor outcomes and should be further validated as a standard end point of chemoimmunotherapy trials of untreated FL. This high-risk FL population warrants further study in directed prospective clinical trials.
authors.affiliation: Carla Casulo and Jonathan W. Friedberg, University of Rochester, Rochester; Jonathan W. Friedberg, Memorial Sloan Kettering Cancer Center, New York, NY; Michelle Byrtek and Keith L. Dawson, Genentech, South San Francisco, CA; Xiaolei Zhou, RTI Health Solutions, Research Triangle Park, NC; Charles M. Farber, Carol G. Simon Cancer Center, Morristown, NJ; Christopher R. Flowers, Emory University, Atlanta, GA; John D. Hainsworth, Sarah Cannon Research Institute, Nashville, TN; Matthew J. Maurer and James R. Cerhan, Mayo Clinic, Rochester, MN; and Brian K. Link, University of Iowa, Iowa City, IA.
authors.forename: Carla
authors.initials: C
authors.lastname: Casulo
authors.affiliation: Carla Casulo and Jonathan W. Friedberg, University of Rochester, Rochester; Jonathan W. Friedberg, Memorial Sloan Kettering Cancer Center, New York, NY; Michelle Byrtek and Keith L. Dawson, Genentech, South San Francisco, CA; Xiaolei Zhou, RTI Health Solutions, Research Triangle Park, NC; Charles M. Farber, Carol G. Simon Cancer Center, Morristown, NJ; Christopher R. Flowers, Emory University, Atlanta, GA; John D. Hainsworth, Sarah Cannon Research Institute, Nashville, TN; Matthew J. Maurer and James R. Cerhan, Mayo Clinic, Rochester, MN; and Brian K. Link, University of Iowa, Iowa City, IA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Byrtek
authors.affiliation: Carla Casulo and Jonathan W. Friedberg, University of Rochester, Rochester; Jonathan W. Friedberg, Memorial Sloan Kettering Cancer Center, New York, NY; Michelle Byrtek and Keith L. Dawson, Genentech, South San Francisco, CA; Xiaolei Zhou, RTI Health Solutions, Research Triangle Park, NC; Charles M. Farber, Carol G. Simon Cancer Center, Morristown, NJ; Christopher R. Flowers, Emory University, Atlanta, GA; John D. Hainsworth, Sarah Cannon Research Institute, Nashville, TN; Matthew J. Maurer and James R. Cerhan, Mayo Clinic, Rochester, MN; and Brian K. Link, University of Iowa, Iowa City, IA.
authors.forename: Keith L
authors.initials: KL
authors.lastname: Dawson
authors.affiliation: Carla Casulo and Jonathan W. Friedberg, University of Rochester, Rochester; Jonathan W. Friedberg, Memorial Sloan Kettering Cancer Center, New York, NY; Michelle Byrtek and Keith L. Dawson, Genentech, South San Francisco, CA; Xiaolei Zhou, RTI Health Solutions, Research Triangle Park, NC; Charles M. Farber, Carol G. Simon Cancer Center, Morristown, NJ; Christopher R. Flowers, Emory University, Atlanta, GA; John D. Hainsworth, Sarah Cannon Research Institute, Nashville, TN; Matthew J. Maurer and James R. Cerhan, Mayo Clinic, Rochester, MN; and Brian K. Link, University of Iowa, Iowa City, IA.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Carla Casulo and Jonathan W. Friedberg, University of Rochester, Rochester; Jonathan W. Friedberg, Memorial Sloan Kettering Cancer Center, New York, NY; Michelle Byrtek and Keith L. Dawson, Genentech, South San Francisco, CA; Xiaolei Zhou, RTI Health Solutions, Research Triangle Park, NC; Charles M. Farber, Carol G. Simon Cancer Center, Morristown, NJ; Christopher R. Flowers, Emory University, Atlanta, GA; John D. Hainsworth, Sarah Cannon Research Institute, Nashville, TN; Matthew J. Maurer and James R. Cerhan, Mayo Clinic, Rochester, MN; and Brian K. Link, University of Iowa, Iowa City, IA.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Farber
authors.affiliation: Carla Casulo and Jonathan W. Friedberg, University of Rochester, Rochester; Jonathan W. Friedberg, Memorial Sloan Kettering Cancer Center, New York, NY; Michelle Byrtek and Keith L. Dawson, Genentech, South San Francisco, CA; Xiaolei Zhou, RTI Health Solutions, Research Triangle Park, NC; Charles M. Farber, Carol G. Simon Cancer Center, Morristown, NJ; Christopher R. Flowers, Emory University, Atlanta, GA; John D. Hainsworth, Sarah Cannon Research Institute, Nashville, TN; Matthew J. Maurer and James R. Cerhan, Mayo Clinic, Rochester, MN; and Brian K. Link, University of Iowa, Iowa City, IA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Flowers
authors.affiliation: Carla Casulo and Jonathan W. Friedberg, University of Rochester, Rochester; Jonathan W. Friedberg, Memorial Sloan Kettering Cancer Center, New York, NY; Michelle Byrtek and Keith L. Dawson, Genentech, South San Francisco, CA; Xiaolei Zhou, RTI Health Solutions, Research Triangle Park, NC; Charles M. Farber, Carol G. Simon Cancer Center, Morristown, NJ; Christopher R. Flowers, Emory University, Atlanta, GA; John D. Hainsworth, Sarah Cannon Research Institute, Nashville, TN; Matthew J. Maurer and James R. Cerhan, Mayo Clinic, Rochester, MN; and Brian K. Link, University of Iowa, Iowa City, IA.
authors.forename: John D
authors.initials: JD
authors.lastname: Hainsworth
authors.affiliation: Carla Casulo and Jonathan W. Friedberg, University of Rochester, Rochester; Jonathan W. Friedberg, Memorial Sloan Kettering Cancer Center, New York, NY; Michelle Byrtek and Keith L. Dawson, Genentech, South San Francisco, CA; Xiaolei Zhou, RTI Health Solutions, Research Triangle Park, NC; Charles M. Farber, Carol G. Simon Cancer Center, Morristown, NJ; Christopher R. Flowers, Emory University, Atlanta, GA; John D. Hainsworth, Sarah Cannon Research Institute, Nashville, TN; Matthew J. Maurer and James R. Cerhan, Mayo Clinic, Rochester, MN; and Brian K. Link, University of Iowa, Iowa City, IA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Maurer
authors.affiliation: Carla Casulo and Jonathan W. Friedberg, University of Rochester, Rochester; Jonathan W. Friedberg, Memorial Sloan Kettering Cancer Center, New York, NY; Michelle Byrtek and Keith L. Dawson, Genentech, South San Francisco, CA; Xiaolei Zhou, RTI Health Solutions, Research Triangle Park, NC; Charles M. Farber, Carol G. Simon Cancer Center, Morristown, NJ; Christopher R. Flowers, Emory University, Atlanta, GA; John D. Hainsworth, Sarah Cannon Research Institute, Nashville, TN; Matthew J. Maurer and James R. Cerhan, Mayo Clinic, Rochester, MN; and Brian K. Link, University of Iowa, Iowa City, IA.
authors.forename: James R
authors.initials: JR
authors.lastname: Cerhan
authors.affiliation: Carla Casulo and Jonathan W. Friedberg, University of Rochester, Rochester; Jonathan W. Friedberg, Memorial Sloan Kettering Cancer Center, New York, NY; Michelle Byrtek and Keith L. Dawson, Genentech, South San Francisco, CA; Xiaolei Zhou, RTI Health Solutions, Research Triangle Park, NC; Charles M. Farber, Carol G. Simon Cancer Center, Morristown, NJ; Christopher R. Flowers, Emory University, Atlanta, GA; John D. Hainsworth, Sarah Cannon Research Institute, Nashville, TN; Matthew J. Maurer and James R. Cerhan, Mayo Clinic, Rochester, MN; and Brian K. Link, University of Iowa, Iowa City, IA.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Link
authors.affiliation: Carla Casulo and Jonathan W. Friedberg, University of Rochester, Rochester; Jonathan W. Friedberg, Memorial Sloan Kettering Cancer Center, New York, NY; Michelle Byrtek and Keith L. Dawson, Genentech, South San Francisco, CA; Xiaolei Zhou, RTI Health Solutions, Research Triangle Park, NC; Charles M. Farber, Carol G. Simon Cancer Center, Morristown, NJ; Christopher R. Flowers, Emory University, Atlanta, GA; John D. Hainsworth, Sarah Cannon Research Institute, Nashville, TN; Matthew J. Maurer and James R. Cerhan, Mayo Clinic, Rochester, MN; and Brian K. Link, University of Iowa, Iowa City, IA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Zelenetz
authors.affiliation: Carla Casulo and Jonathan W. Friedberg, University of Rochester, Rochester; Jonathan W. Friedberg, Memorial Sloan Kettering Cancer Center, New York, NY; Michelle Byrtek and Keith L. Dawson, Genentech, South San Francisco, CA; Xiaolei Zhou, RTI Health Solutions, Research Triangle Park, NC; Charles M. Farber, Carol G. Simon Cancer Center, Morristown, NJ; Christopher R. Flowers, Emory University, Atlanta, GA; John D. Hainsworth, Sarah Cannon Research Institute, Nashville, TN; Matthew J. Maurer and James R. Cerhan, Mayo Clinic, Rochester, MN; and Brian K. Link, University of Iowa, Iowa City, IA. jonathan_friedberg@urmc.rochester.edu.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Friedberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality*; D016017:Odds Ratio; D011241:Prednisone / Q000008:administration & dosage; D018570:Risk Assessment; D012307:Risk Factors; D000069283:Rituximab; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone