TY - JOUR
T1 - Flipi24
T2 - A Modern Prognostic Model and Clinical Trial Enrichment Tool for Newly Diagnosed Follicular Lymphoma
AU - Maurer, Matthew J
AU - Prochazka, Vit K
AU - El-Galaly, Tarec Christoffer
AU - Flowers, Christopher R
AU - Villa, Diego
AU - Bachy, Emmanuel
AU - Cahn, Elliot J
AU - Fournier, Marguerite
AU - Larson, Melissa C
AU - Dietrich, Caroline E
AU - Jakobsen, Lasse Hjort
AU - Ghesquières, Hervé
AU - Kridel, Robert
AU - Gandhi, Maher K
AU - Cheah, Chan Y
AU - Hawkes, Eliza A
AU - Seymour, John F
AU - Freeman, Ciara L
AU - Clausen, Michael R
AU - Wahlin, Björn E
AU - Friedberg, Jonathan W
AU - Casulo, Carla
AU - Habermann, Thomas M
AU - Wang, Yucai
AU - Nastoupil, Loretta J
AU - de Nully Brown, Peter
AU - Belada, David
AU - Janíková, Andrea
AU - Mocikova, Heidi
AU - Fürst, Tomáš
AU - Feugier, Pierre
AU - Tilly, Hervé
AU - Haioun, Corinne
AU - Davies, Andrew J
AU - Cartron, Guillaume
AU - Burack, Richard
AU - Chihara, Dai
AU - Martin, Peter
AU - Cohen, Jonathon B
AU - Lossos, Izidore S
AU - Kahl, Brad S
AU - Sehn, Laurie H
AU - Smedby, Karin E
AU - Salles, Gilles
AU - Trneny, Marek
AU - Link, Brian K
AU - Morschhauser, Franck
AU - Cerhan, James R
PY - 2026/1/10
Y1 - 2026/1/10
N2 - 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.
AB - 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.
KW - Humans
KW - Lymphoma, Follicular/mortality
KW - Male
KW - Female
KW - Middle Aged
KW - Aged
KW - Prognosis
KW - Prospective Studies
KW - Risk Assessment
KW - Adult
KW - Clinical Trials, Phase III as Topic
KW - Randomized Controlled Trials as Topic
KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
UR - https://www.scopus.com/pages/publications/105027168499
U2 - 10.1200/JCO-25-00892
DO - 10.1200/JCO-25-00892
M3 - Journal article
C2 - 41329901
SN - 0732-183X
VL - 44
SP - 117
EP - 128
JO - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
IS - 2
ER -