title: Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy.
abstract: OBJECTIVE
  Studies of diffuse large B-cell lymphoma (DLBCL) are typically evaluated by using a time-to-event approach with relapse, re-treatment, and death commonly used as the events. We evaluated the timing and type of events in newly diagnosed DLBCL and compared patient outcome with reference population data.
  
  
  METHODS
  Patients with newly diagnosed DLBCL treated with immunochemotherapy were prospectively enrolled onto the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource (MER) and the North Central Cancer Treatment Group NCCTG-N0489 clinical trial from 2002 to 2009. Patient outcomes were evaluated at diagnosis and in the subsets of patients achieving event-free status at 12 months (EFS12) and 24 months (EFS24) from diagnosis. Overall survival was compared with age- and sex-matched population data. Results were replicated in an external validation cohort from the Groupe d'Etude des Lymphomes de l'Adulte (GELA) Lymphome Non Hodgkinien 2003 (LNH2003) program and a registry based in Lyon, France.
  
  
  RESULTS
  In all, 767 patients with newly diagnosed DLBCL who had a median age of 63 years were enrolled onto the MER and NCCTG studies. At a median follow-up of 60 months (range, 8 to 116 months), 299 patients had an event and 210 patients had died. Patients achieving EFS24 had an overall survival equivalent to that of the age- and sex-matched general population (standardized mortality ratio [SMR], 1.18; P = .25). This result was confirmed in 820 patients from the GELA study and registry in Lyon (SMR, 1.09; P = .71). Simulation studies showed that EFS24 has comparable power to continuous EFS when evaluating clinical trials in DLBCL.
  
  
  CONCLUSIONS
  Patients with DLBCL who achieve EFS24 have a subsequent overall survival equivalent to that of the age- and sex-matched general population. EFS24 will be useful in patient counseling and should be considered as an end point for future studies of newly diagnosed DLBCL.
authors.affiliation: Matthew J. Maurer, Hervé Ghesquières, Thomas E. Witzig, Carrie A. Thompson, Ivana N. Micallef, William R. Macon, Paul J. Kurtin, Cristine Allmer, Susan L. Slager, Thomas M. Habermann, and James R. Cerhan, Mayo Clinic, Rochester, MN; Hervé Ghesquières and Emmanuelle Nicolas-Virelizier, Centre Léon Bérard; Hervé Ghesquières and Gilles Salles, Université Claude Bernard, Unite Mixte de Recherche (UMR), Centre National de la Recherche Scientifique 5239, Lyon; Jean-Philippe Jais, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR S 872, Necker Hospital, Assistance Publique-Hopitaux de Paris; Richard Delarue, Necker Hospital; Thierry Jo Molina, Paris Descartes University, Paris Centre University Hospital, Paris; Corinne Haioun, Henri Mondor Hospital, Université Paris-Est, Créteil; Frédéric Peyrade, Centre Antoine Lacassagne, Nice; Olivier Fitoussi, Polyclinique Bordeaux-Nord, Bordeaux; Gilles Salles, Hospices Civils de Lyon, Pierre Benite; Hervé Tilly, INSERM U918, Institute for Research and Innovation in Biomedicine, Centre Henri Becquerel, Rouen, France; Nicolas Ketterer, Lausanne Hospital, Lausanne, Switzerland; and Sergei I. Syrbu and Brian K. Link, University of Iowa College of Medicine, Iowa City, IA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Maurer
authors.forename: Hervé
authors.initials: H
authors.lastname: Ghesquières
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Jais
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Witzig
authors.forename: Corinne
authors.initials: C
authors.lastname: Haioun
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Thompson
authors.forename: Richard
authors.initials: R
authors.lastname: Delarue
authors.forename: Ivana N
authors.initials: IN
authors.lastname: Micallef
authors.forename: Frédéric
authors.initials: F
authors.lastname: Peyrade
authors.forename: William R
authors.initials: WR
authors.lastname: Macon
authors.forename: Thierry
authors.initials: T
authors.lastname: Jo Molina
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ketterer
authors.forename: Sergei I
authors.initials: SI
authors.lastname: Syrbu
authors.forename: Olivier
authors.initials: O
authors.lastname: Fitoussi
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kurtin
authors.forename: Cristine
authors.initials: C
authors.lastname: Allmer
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Nicolas-Virelizier
authors.forename: Susan L
authors.initials: SL
authors.lastname: Slager
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Habermann
authors.forename: Brian K
authors.initials: BK
authors.lastname: Link
authors.forename: Gilles
authors.initials: G
authors.lastname: Salles
authors.forename: Hervé
authors.initials: H
authors.lastname: Tilly
authors.forename: James R
authors.initials: JR
authors.lastname: Cerhan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016022:Case-Control Studies; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D000069283:Rituximab; D013997:Time Factors; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab