Subsets of follicular lymphoma 3B have divergent outcomes: results from the prospective multicenter MER and LEO cohorts

Abstract Follicular lymphoma (FL) 3B is considered an aggressive lymphoma, however recent studies have challenged this paradigm. Additional controversy involves the clinical implication of pure FL3B (FL3Bp) vs FL3B with concurrent diffuse large B cell lymphoma (DLBCL) (FL3Bc). To address these quest...

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Main Authors: Patrizia Mondello, Brianna Negaard, Andrew L. Feldman, Brian K. Link, Carla Casulo, Dai Chihara, David Russler-Germain, Jason Romancik, Caitlin Gribbin, Sara Haddadi, Eric Mou, Ivana N. Micallef, Patrick B. Johnston, Joseph Novak, Yucai Wang, Rebecca L. King, Anne J. Novak, Thomas M. Habermann, Peter Martin, Brad Kahl, Grzegorz S. Nowakowski, Loretta J. Nastoupil, James R. Cerhan, Christopher R. Flowers, Izidore S. Lossos, Richard W. Burack, Matthew J. Maurer, Stephen M. Ansell
Format: Article
Language:English
Published: Nature Publishing Group 2025-08-01
Series:Blood Cancer Journal
Online Access:https://doi.org/10.1038/s41408-025-01347-0
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author Patrizia Mondello
Brianna Negaard
Andrew L. Feldman
Brian K. Link
Carla Casulo
Dai Chihara
David Russler-Germain
Jason Romancik
Caitlin Gribbin
Sara Haddadi
Eric Mou
Ivana N. Micallef
Patrick B. Johnston
Joseph Novak
Yucai Wang
Rebecca L. King
Anne J. Novak
Thomas M. Habermann
Peter Martin
Brad Kahl
Grzegorz S. Nowakowski
Loretta J. Nastoupil
James R. Cerhan
Christopher R. Flowers
Izidore S. Lossos
Richard W. Burack
Matthew J. Maurer
Stephen M. Ansell
author_facet Patrizia Mondello
Brianna Negaard
Andrew L. Feldman
Brian K. Link
Carla Casulo
Dai Chihara
David Russler-Germain
Jason Romancik
Caitlin Gribbin
Sara Haddadi
Eric Mou
Ivana N. Micallef
Patrick B. Johnston
Joseph Novak
Yucai Wang
Rebecca L. King
Anne J. Novak
Thomas M. Habermann
Peter Martin
Brad Kahl
Grzegorz S. Nowakowski
Loretta J. Nastoupil
James R. Cerhan
Christopher R. Flowers
Izidore S. Lossos
Richard W. Burack
Matthew J. Maurer
Stephen M. Ansell
author_sort Patrizia Mondello
collection DOAJ
description Abstract Follicular lymphoma (FL) 3B is considered an aggressive lymphoma, however recent studies have challenged this paradigm. Additional controversy involves the clinical implication of pure FL3B (FL3Bp) vs FL3B with concurrent diffuse large B cell lymphoma (DLBCL) (FL3Bc). To address these questions, we performed a pooled study of the MER and LEO cohorts comparing 464 newly diagnosed, R-CHOP-treated patients with FL1-2 (n = 216), FL3A (n = 170), FL3B (n = 78) and 739 DLBCL. Among FL3B patients, 19 (24%) had FL3Bc and 59 (76%) FL3Bp. Baseline characteristics and outcomes were similar between the two FL3B subtypes. Compared to FL1-3A, FL3B showed similar clinical features, except for a lower tumor burden. After R-CHOP, FL1-2 patients had an inferior event-free survival (EFS) than those with FL3B, whereas there was no difference with FL3A. Survival was similar across the FL grades. Although FL1-2 patients failed to achieve EFS24 more frequently than FL3B and FL3A, FL3B patients who failed EFS24 had three-fold higher risk of subsequent mortality than other FLs. At 5-year follow-up FL3B patients had twice the risk of relapse with an aggressive subtype than those with FL1-2 and FL3A. Compared to DLBCL, FL3B patients had more favorable clinical features, but similar outcomes to GCB subtype. Our data suggest that most FL3B have a good outcome, while a subset has an aggressive behavior.
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spelling doaj-art-1a987d82bba346e6ac20404601683da52025-08-20T04:01:47ZengNature Publishing GroupBlood Cancer Journal2044-53852025-08-011511810.1038/s41408-025-01347-0Subsets of follicular lymphoma 3B have divergent outcomes: results from the prospective multicenter MER and LEO cohortsPatrizia Mondello0Brianna Negaard1Andrew L. Feldman2Brian K. Link3Carla Casulo4Dai Chihara5David Russler-Germain6Jason Romancik7Caitlin Gribbin8Sara Haddadi9Eric Mou10Ivana N. Micallef11Patrick B. Johnston12Joseph Novak13Yucai Wang14Rebecca L. King15Anne J. Novak16Thomas M. Habermann17Peter Martin18Brad Kahl19Grzegorz S. Nowakowski20Loretta J. Nastoupil21James R. Cerhan22Christopher R. Flowers23Izidore S. Lossos24Richard W. Burack25Matthew J. Maurer26Stephen M. Ansell27Division of Hematology, Mayo ClinicDepartment of Quantitative Health Sciences, Mayo ClinicDivision of Hematopathology, Mayo ClinicDivision of Hematology, Oncology and Bone Marrow Transplantation, University of IowaWilmot Cancer Institute, University of RochesterMD Anderson Cancer CenterWashington University School of Medicine in St LouisDepartment of Hematology and Medical Oncology, Winship Cancer Institute at Emory UniversityWeill Cornell Medical CollegeDivision of Hematology, Sylvester Comprehensive Cancer Center, University of MiamiDivision of Hematology, Oncology and Bone Marrow Transplantation, University of IowaDivision of Hematology, Mayo ClinicDivision of Hematology, Mayo ClinicDivision of Hematology, Mayo ClinicDivision of Hematology, Mayo ClinicDivision of Hematopathology, Mayo ClinicDivision of Hematology, Mayo ClinicDivision of Hematology, Mayo ClinicWeill Cornell Medical CollegeWashington University School of Medicine in St LouisDivision of Hematology, Mayo ClinicMD Anderson Cancer CenterDepartment of Quantitative Health Sciences, Mayo ClinicMD Anderson Cancer CenterDivision of Hematology, Sylvester Comprehensive Cancer Center, University of MiamiWilmot Cancer Institute, University of RochesterDepartment of Quantitative Health Sciences, Mayo ClinicDivision of Hematology, Mayo ClinicAbstract Follicular lymphoma (FL) 3B is considered an aggressive lymphoma, however recent studies have challenged this paradigm. Additional controversy involves the clinical implication of pure FL3B (FL3Bp) vs FL3B with concurrent diffuse large B cell lymphoma (DLBCL) (FL3Bc). To address these questions, we performed a pooled study of the MER and LEO cohorts comparing 464 newly diagnosed, R-CHOP-treated patients with FL1-2 (n = 216), FL3A (n = 170), FL3B (n = 78) and 739 DLBCL. Among FL3B patients, 19 (24%) had FL3Bc and 59 (76%) FL3Bp. Baseline characteristics and outcomes were similar between the two FL3B subtypes. Compared to FL1-3A, FL3B showed similar clinical features, except for a lower tumor burden. After R-CHOP, FL1-2 patients had an inferior event-free survival (EFS) than those with FL3B, whereas there was no difference with FL3A. Survival was similar across the FL grades. Although FL1-2 patients failed to achieve EFS24 more frequently than FL3B and FL3A, FL3B patients who failed EFS24 had three-fold higher risk of subsequent mortality than other FLs. At 5-year follow-up FL3B patients had twice the risk of relapse with an aggressive subtype than those with FL1-2 and FL3A. Compared to DLBCL, FL3B patients had more favorable clinical features, but similar outcomes to GCB subtype. Our data suggest that most FL3B have a good outcome, while a subset has an aggressive behavior.https://doi.org/10.1038/s41408-025-01347-0
spellingShingle Patrizia Mondello
Brianna Negaard
Andrew L. Feldman
Brian K. Link
Carla Casulo
Dai Chihara
David Russler-Germain
Jason Romancik
Caitlin Gribbin
Sara Haddadi
Eric Mou
Ivana N. Micallef
Patrick B. Johnston
Joseph Novak
Yucai Wang
Rebecca L. King
Anne J. Novak
Thomas M. Habermann
Peter Martin
Brad Kahl
Grzegorz S. Nowakowski
Loretta J. Nastoupil
James R. Cerhan
Christopher R. Flowers
Izidore S. Lossos
Richard W. Burack
Matthew J. Maurer
Stephen M. Ansell
Subsets of follicular lymphoma 3B have divergent outcomes: results from the prospective multicenter MER and LEO cohorts
Blood Cancer Journal
title Subsets of follicular lymphoma 3B have divergent outcomes: results from the prospective multicenter MER and LEO cohorts
title_full Subsets of follicular lymphoma 3B have divergent outcomes: results from the prospective multicenter MER and LEO cohorts
title_fullStr Subsets of follicular lymphoma 3B have divergent outcomes: results from the prospective multicenter MER and LEO cohorts
title_full_unstemmed Subsets of follicular lymphoma 3B have divergent outcomes: results from the prospective multicenter MER and LEO cohorts
title_short Subsets of follicular lymphoma 3B have divergent outcomes: results from the prospective multicenter MER and LEO cohorts
title_sort subsets of follicular lymphoma 3b have divergent outcomes results from the prospective multicenter mer and leo cohorts
url https://doi.org/10.1038/s41408-025-01347-0
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