title: Early event status informs subsequent outcome in newly diagnosed follicular lymphoma.
abstract: Recent advances in follicular lymphoma (FL) have resulted in prolongation of overall survival (OS). Here we assessed if early events as defined by event-free survival (EFS) at 12 and 24 months from diagnosis (EFS12/EFS24) can inform subsequent OS in FL. 920 newly diagnosed grade 1-3A FL patients enrolled on the University of Iowa/Mayo Clinic Lymphoma SPORE Molecular Epidemiology Resource (MER) from 2002-2012 were initially evaluated. EFS was defined as time from diagnosis to progression, relapse, re-treatment, or death due to any cause. OS was compared to age-and-sex-matched survival in the general US population using standardized mortality ratios (SMR) and 95% confidence intervals (CI). We used a cohort of 412 FL patients from two Lyon, France hospital registries for independent replication. Patients who failed to achieve EFS12 had poor subsequent OS (MER SMR = 3.72, 95%CI: 2.78-4.88; Lyon SMR = 8.74, 95%CI: 5.41-13.36). Conversely, patients achieving EFS12 had no added mortality beyond the background population (MER SMR = 0.73, 95%CI: 0.56-0.94, Lyon SMR = 1.02, 95%CI: 0.58-1.65). Patients with early events after immunochemotherapy had especially poor outcomes (EFS12 failure: MER SMR = 17.63, 95%CI:11.97-25.02, Lyon SMR = 19.10, 95%CI:9.86-33.36; EFS24 failure: MER SMR = 13.02, 95%CI:9.31-17.74, Lyon SMR = 7.22, 95%CI:4.13-11.74). In a combined dataset of all patients from both cohorts, baseline FLIPI was no longer informative in EFS12 achievers. Reassessment of patient status at 12 months from diagnosis in follicular lymphoma patients, or at 24 months in patients treated with immunochemotherapy, is a strong predictor of subsequent overall survival in FL. Early event status provides a simple, clinically relevant endpoint for studies assessing outcome in FL. Am. J. Hematol. 91:1096-1101, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota. maurer@mayo.Edu.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Maurer
authors.affiliation: Department of Hematology, Hospices Civils De Lyon, Centre Hospitalier Lyon-Sud and Université Claude Bernard, Lyon, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bachy
authors.affiliation: Department of Hematology, Hospices Civils De Lyon, Centre Hospitalier Lyon-Sud and Université Claude Bernard, Lyon, France.|Department of Medical Oncology, Centre Léon Bérard, Lyon, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Ghesquières
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Ansell
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Grzegorz S
authors.initials: GS
authors.lastname: Nowakowski
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Thompson
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: David J
authors.initials: DJ
authors.lastname: Inwards
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Cristine
authors.initials: C
authors.lastname: Allmer
authors.affiliation: Department of Pathology, Centre Léon Bérard, Lyon, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Chassagne-Clément
authors.affiliation: Department of Medical Oncology, Centre Léon Bérard, Lyon, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Nicolas-Virelizier
authors.affiliation: Department of Medical Oncology, Centre Léon Bérard, Lyon, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Sebban
authors.affiliation: Department of Hematology, Hospices Civils De Lyon, Centre Hospitalier Lyon-Sud and Université Claude Bernard, Lyon, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Lebras
authors.affiliation: Department of Hematology, Hospices Civils De Lyon, Centre Hospitalier Lyon-Sud and Université Claude Bernard, Lyon, France.
authors.forename: Clementine
authors.initials: C
authors.lastname: Sarkozy
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: William R
authors.initials: WR
authors.lastname: Macon
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Feldman
authors.affiliation: Department of Pathology, University of Iowa, Iowa City, IA.
authors.forename: Sergei I
authors.initials: SI
authors.lastname: Syrbu
authors.affiliation: Department of Pathology, Hospices Civils De Lyon, Centre Hospitalier Lyon-Sud and Université Claude Bernard, Lyon, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Traverse-Glehan
authors.affiliation: Department of Hematology, Hospices Civils De Lyon, Centre Hospitalier Lyon-Sud and Université Claude Bernard, Lyon, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Coiffier
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Slager
authors.affiliation: Department of Hematology, Oncology and Blood and Marrow Transplantation, University of Iowa, Iowa City, IA.
authors.forename: George J
authors.initials: GJ
authors.lastname: Weiner
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Witzig
authors.affiliation: Department of Hematology, Hospices Civils De Lyon, Centre Hospitalier Lyon-Sud and Université Claude Bernard, Lyon, France.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Habermann
authors.affiliation: Department of Hematology, Hospices Civils De Lyon, Centre Hospitalier Lyon-Sud and Université Claude Bernard, Lyon, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Salles
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: James R
authors.initials: JR
authors.lastname: Cerhan
authors.affiliation: Department of Hematology, Oncology and Blood and Marrow Transplantation, University of Iowa, Iowa City, IA.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Link
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008224:Lymphoma, Follicular / Q000175:diagnosis* / Q000453:epidemiology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012042:Registries; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult