FLIPI24: A Modern Prognostic Model and Clinical Trial Enrichment Tool for Newly Diagnosed Follicular Lymphoma
Abstract
PURPOSE Although most patients with follicular lymphoma (FL) can expect an indolent course, progressive lymphoma remains the primary cause of death during the first decade after diagnosis. Progression of disease within 24 months (POD24) of starting first-line (1L) immunochemotherapy defines a high-risk population with poor survival, but better risk stratification at diagnosis is needed. METHODS The FLIPI24 model was developed and internally validated to predict 24-month event rates using individual data from 4,485 patients treated with 1L immunochemotherapy from 10 observational cohorts of FL. Overall and cause-specific survival was further evaluated in FLIPI24 risk groups. External validation in the 1L immunochemotherapy setting was performed using the prospective observational Lymphoma Epidemiology of Outcomes (LEO) cohort (N = 565) and three randomized phase III trials (N = 3,192); extension to all patients with FL (any 1L therapy) was performed in the LEO cohort (N = 1,445) and its Molecular Epidemiology Resource subcohort (N = 1,074). RESULTS The FLIPI24 model uses age and four blood-based variables (hemoglobin, lactate dehydrogenase, beta-2 microglobulin, and WBC count). FLIPI24 showed consistent performance across validation and extension data sets, which was superior to existing prognostic tools. Across the four external immunochemotherapy validation data sets, patients with high-risk FLIPI24 (23%-32% of patients) had significantly higher 24-month event rates (22%-35%) and inferior 5-year overall survival (77%-83%) compared with patients with low-risk FLIPI24 (29%-31% of patients, 24-month event rates: 10%-12%; 5-year OS: 96%-97%). Results were consistent when evaluating lymphoma-related death and when extended to all patients with FL. CONCLUSION The FLIPI24 model robustly stratifies, at diagnosis, patients with FL at increased risk of lymphoma-related death versus patients with very low lymphoma-related mortality during the first decade after diagnosis. FLIPI24 can be used to enrich future clinical trial designs in newly diagnosed FL.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (48)
Matthew J. Maurer
2Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN
Vit K. Prochazka
Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc, Olomouc, Czech Republic
Tarec Christoffer El-Galaly
3Departments of Hematology, Clinical Epidemiology, and Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
Christopher R. Flowers
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine
Diego Villa
8Division of Medical Oncology, BC Cancer Centre for Lymphoid Cancer and The University of British Columbia, Vancouver, Canada
Emmanuel Bachy
Elliot J. Cahn
2Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN
Marguerite Fournier
19LYSARC, Pierre Benite, France
Melissa C. Larson
2Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN
Caroline E. Dietrich
5Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
Lasse Hjort Jakobsen
Department of Hematology, Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark
Hervé Ghesquieres
Hopital Lyon Sud, Claude Bernard Lyon 1 University, Pierre-Benite, France
Robert Kridel
Princess Margaret Cancer Centre, Toronto
Maher K. Gandhi
17Translational Research Institute, Mater Research Institute University of Queensland, Brisbane, QLD, Australia
Chan Y. Cheah
12Department of Haematology, Sir Charles Gairdner Hospital, Perth, Australia
Eliza A. Hawkes
14Olivia Newton-John Cancer Research Institute, Austin Health, Melbourne, Australia
John F. Seymour
Department of Haematology, Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
Ciara L. Freeman
7Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Michael R. Clausen
10Department of Medicine, Vejle Hospital, Vejle, Denmark
Björn E. Wahlin
11Division of Haematology, Department of Medicine at Huddinge, Karolinska Institutet, Stockholm, Sweden
Jonathan W. Friedberg
18Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY
Carla Casulo
18Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY
Thomas M. Habermann
22Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN
Yucai Wang
State Key Laboratory of Immune Response and Immunotherapy, Department of Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine
Loretta J. Nastoupil
Peter de Nully Brown
23Department of Hematology, Rigshospitalet, Copenhagen, Denmark
David Belada
4th Department of Internal Medicine - Haematology, University Hospital and Faculty of Medicine, Hradec Kralove, Czech Republic
Andrea Janíková
26Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
Heidi Mocikova
Tomáš Fürst
Faculty of Science, Palacky University Olomouc, Olomouc, Czech Republic
Pierre Feugier
2Service Hématologie, Centre Hospitalier Régional Universitaire de Nancy–Hôpital Brabois, Université de Lorraine, Nancy, France
Hervé Tilly
5Service Hématologie, Centre Henri Becquerel, Rouen, France
Corinne Haioun
4Hematology Department, Hôpital Henri Mondor, APHP, Creteil, France
Andrew J. Davies
1School of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
Guillaume Cartron
CHU Montpellier UMR5535, Montpellier, France
Richard Burack
Dai Chihara
Peter Martin
Jonathon B. Cohen
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine
Izidore S. Lossos
29Division of Hematology, Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL
Brad S. Kahl
30Division of Oncology, Washington University School of Medicine, St. Louis, MO
Laurie H. Sehn
8Division of Medical Oncology, BC Cancer Centre for Lymphoid Cancer and The University of British Columbia, Vancouver, Canada
Karin E. Smedby
5Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
Gilles Salles
41Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY
Marek Trneny
Brian K. Link
Franck Morschhauser
Centre Hospitalier Universitaire de Lille, Groupe de Recherche sur les formes Injectables et les Technologies Associées, Lille, France
James R. Cerhan