title: Clinicogenetic risk models predict early progression of follicular lymphoma after first-line immunochemotherapy.
abstract: Follicular lymphoma (FL) is a clinically and molecularly heterogeneous disease. Posttreatment surrogate end points, such as progression of disease within 24 months (POD24) are promising predictors for overall survival (OS) but are of limited clinical value, primarily because they cannot guide up-front treatment decisions. We used the clinical and molecular data from 2 independent cohorts of symptomatic patients in need of first-line immunochemotherapy (151 patients from a German Low-Grade Lymphoma Study Group [GLSG] trial and 107 patients from a population-based registry of the British Columbia Cancer Agency [BCCA]) to validate the predictive utility of POD24, and to evaluate the ability of pretreatment risk models to predict early treatment failure. POD24 occurred in 17% and 23% of evaluable GLSG and BCCA patients, with 5-year OS rates of 41% (vs 91% for those without POD24, P < .0001) and 26% (vs 86%, P < .0001), respectively. The m7-FL International Prognostic Index (m7-FLIPI), a prospective clinicogenetic risk model for failure-free survival, had the highest accuracy to predict POD24 (76% and 77%, respectively) with an odds ratio of 5.82 in GLSG (P = .00031) and 4.76 in BCCA patients (P = .0052). A clinicogenetic risk model specifically designed to predict POD24, the POD24-PI, had the highest sensitivity to predict POD24, but at the expense of a lower specificity. In conclusion, the m7-FLIPI prospectively identifies the smallest subgroup of patients (28% and 22%, respectively) at highest risk of early failure of first-line immunochemotherapy and death, including patients not fulfilling the POD24 criteria, and should be evaluated in prospective trials of precision medicine approaches in FL.
authors.affiliation: Medical Department III, University Hospital of the Ludwig Maximilians University Munich, Munich, Germany; Institute for Medical Informatics, Biometry and Epidemiology, Ludwig Maximilians University Munich, Munich, Germany;
authors.forename: Vindi
authors.initials: V
authors.lastname: Jurinovic
authors.affiliation: Centre for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, BC, Canada;
authors.forename: Robert
authors.initials: R
authors.lastname: Kridel
authors.affiliation: Department of Clinical Pathology, Robert-Bosch-Krankenhaus, Stuttgart, Germany; Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University of Tübingen, Tübingen, Germany;
authors.forename: Annette M
authors.initials: AM
authors.lastname: Staiger
authors.affiliation: Hematopathology Section, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany;
authors.forename: Monika
authors.initials: M
authors.lastname: Szczepanowski
authors.affiliation: Department of Clinical Pathology, Robert-Bosch-Krankenhaus, Stuttgart, Germany; Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University of Tübingen, Tübingen, Germany;
authors.forename: Heike
authors.initials: H
authors.lastname: Horn
authors.affiliation: Medical Department III, University Hospital of the Ludwig Maximilians University Munich, Munich, Germany;
authors.forename: Martin H
authors.initials: MH
authors.lastname: Dreyling
authors.affiliation: Institute of Pathology, University of Würzburg, and Comprehensive Cancer Center Mainfranken, Würzburg, Germany;
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.affiliation: Department of Clinical Pathology, Robert-Bosch-Krankenhaus, Stuttgart, Germany;
authors.forename: German
authors.initials: G
authors.lastname: Ott
authors.affiliation: Hematopathology Section, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany;
authors.forename: Wolfram
authors.initials: W
authors.lastname: Klapper
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, and Weill Medical College of Cornell University, New York, NY;
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Zelenetz
authors.affiliation: Wilmot Cancer Institute, University of Rochester, Rochester NY;
authors.forename: Paul M
authors.initials: PM
authors.lastname: Barr
authors.affiliation: Wilmot Cancer Institute, University of Rochester, Rochester NY;
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Friedberg
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN;
authors.forename: Stephen
authors.initials: S
authors.lastname: Ansell
authors.affiliation: Centre for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, BC, Canada;
authors.forename: Laurie H
authors.initials: LH
authors.lastname: Sehn
authors.affiliation: Centre for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, BC, Canada;
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Connors
authors.affiliation: Centre for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, BC, Canada;
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.affiliation: Medical Department III, University Hospital of the Ludwig Maximilians University Munich, Munich, Germany; German Cancer Consortium and German Cancer Research Center, Heidelberg, Germany; and.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hiddemann
authors.affiliation: Medical Department III, University Hospital of the Ludwig Maximilians University Munich, Munich, Germany;
authors.forename: Michael
authors.initials: M
authors.lastname: Unterhalt
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: David M
authors.initials: DM
authors.lastname: Weinstock
authors.affiliation: Medical Department III, University Hospital of the Ludwig Maximilians University Munich, Munich, Germany; German Cancer Consortium and German Cancer Research Center, Heidelberg, Germany; and.
authors.forename: Oliver
authors.initials: O
authors.lastname: Weigert
mesh_terms: D000328:Adult; D000368:Aged; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D015203:Reproducibility of Results; D012307:Risk Factors; D016019:Survival Analysis