Development and validation of a gene expression signature to predict early events in patients with follicular lymphoma

Although follicular lymphoma (FL) typically follows an indolent course, patients with FL who experience early events, such as transformation or progression, have increased risk of death related to lymphoma. The FL24Cx is an algorithm based on a 45-target gene expression profiling (GEP) assay, which was developed and trained using 265 formalin-fixed, paraffin-embedded tissue samples on a reliable platform to predict, at the time of diagnosis, whether a patient will experience an event within 24 months. The modeling also confirmed and relied upon previously reported synergy between immune response (IR) gene expression signatures IR1 and IR2. Once locked, the 5-factor logistic regression FL24Cx model was independently validated in a retrospectively assessed cohort of 232 patients from 2 immunochemotherapy-treated arms of SWOG Cancer Research Network S0016 phase 3 clinical trial, in which it assigned 169 patients to the low-risk group with 29 events before 24 months (17.2%) and 63 patients to the high-risk group with 24 events before 24 months (38.1%). The relative risk of an event within 24 months after registration among patients who were classified into the high-risk group relative to patients who were classified into the low-risk group was 2.2 (95% confidence interval, 1.41 to 3.51). An up-front GEP biomarker, such as the FL24Cx, rigorously validated in a clinical laboratory and with a clinically relevant turnaround time, could identify and steer enrollment of patients at high risk for early events in clinical trials, thus enabling timely interpretation of such trials and increasing the pace of innovation.

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Publication Details

Journal
Blood Advances
Published
2025-09-18
DOI
https://doi.org/10.1182/bloodadvances.2025016827
Citations
1
Primary Topic
Lymphoma Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
1.47

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article

Development and validation of a gene expression signature to predict early events in patients with follicular lymphoma

Thomas E. Witzig, Sonali M. Smith, David W. Scott, Thomas Matthew Habermann et al.
1 citations
Blood Advances
Lymphoma Diagnosis and Treatment
1.47
article

Development and validation of a gene expression signature to predict early events in patients with follicular lymphoma

Thomas E. Witzig, Sonali M. Smith, David W. Scott, Thomas Matthew Habermann, Louis M. Staudt, Anne J. Novak, Jonathan W. Friedberg, Michael LeBlanc, Colleen Ramsower, Robert Kridel, Christian Steidl, Mazyar Shadman, Allison Rosenthal, Matthew J. Maurer, James R. Cerhan, Brian K. Link, George W. Wright, Raphael Mwangi, Hongli Li, Lisa M. Rimsza
article en
1 citations

Abstract

Although follicular lymphoma (FL) typically follows an indolent course, patients with FL who experience early events, such as transformation or progression, have increased risk of death related to lymphoma. The FL24Cx is an algorithm based on a 45-target gene expression profiling (GEP) assay, which was developed and trained using 265 formalin-fixed, paraffin-embedded tissue samples on a reliable platform to predict, at the time of diagnosis, whether a patient will experience an event within 24 months. The modeling also confirmed and relied upon previously reported synergy between immune response (IR) gene expression signatures IR1 and IR2. Once locked, the 5-factor logistic regression FL24Cx model was independently validated in a retrospectively assessed cohort of 232 patients from 2 immunochemotherapy-treated arms of SWOG Cancer Research Network S0016 phase 3 clinical trial, in which it assigned 169 patients to the low-risk group with 29 events before 24 months (17.2%) and 63 patients to the high-risk group with 24 events before 24 months (38.1%). The relative risk of an event within 24 months after registration among patients who were classified into the high-risk group relative to patients who were classified into the low-risk group was 2.2 (95% confidence interval, 1.41 to 3.51). An up-front GEP biomarker, such as the FL24Cx, rigorously validated in a clinical laboratory and with a clinically relevant turnaround time, could identify and steer enrollment of patients at high risk for early events in clinical trials, thus enabling timely interpretation of such trials and increasing the pace of innovation.

Blood AdvancesVol. 9(24)
University of Iowa (US), National Institutes of Health (US), Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa (ZA), Mayo Clinic (US), University of Arizona (US), University of British Columbia (CA), Spinal Cord Injury BC (CA), WinnMed (US), Princess Margaret Cancer Centre (CA), University of Chicago (US), Fred Hutch Cancer Center (US), Mayo Clinic Hospital (US), National Cancer Institute (US), Mayo Clinic in Florida (US), SWOG Cancer Research Network (US), University of Rochester (US)
Hope Foundation, National Cancer Institute
Openalex Percentile: Top 15%
Lymphoma Diagnosis and Treatment
1.47
DOIOpen Access PDFOpenAlex
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