Journal article
Development and Validation of a Gene Expression Signature to Predict Early Events in Patients with Follicular Lymphoma
Blood advances, Vol.9(24), pp.6443-6454
12/23/2025
DOI: 10.1182/bloodadvances.2025016827
PMCID: PMC12755980
PMID: 40966421
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, if 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 two immunochemotherapy-treated arms of SWOG Cancer Research Network S0016 phase III clinical trial, where it assigned 169 to the low-risk group with 29 events before 24 months (17.2%) and 63 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% CI: 1.41 to 3.51). An upfront GEP biomarker such as the FL24Cx, rigorously validated in a clinical laboratory, with a clinically-relevant turn-around 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.
Details
- Title: Subtitle
- Development and Validation of a Gene Expression Signature to Predict Early Events in Patients with Follicular Lymphoma
- Creators
- Colleen A Ramsower - University of ArizonaGeorge Wright - National Institutes of HealthHongli Li - SWOG Cancer Research NetworkJames R Cerhan - Mayo ClinicMatthew J Maurer - Mayo ClinicRaphael Mwangi - Mayo ClinicAllison C Rosenthal - Mayo Clinic HospitalAnne J Novak - Mayo ClinicBrian K Link - University of IowaThomas E Witzig - Mayo ClinicThomas M Habermann - Mayo ClinicRobert Kridel - Princess Margaret Cancer CentreMichael L LeBlanc - Fred Hutch Cancer CenterMazyar Shadman - Fred Hutch Cancer CenterSonali M Smith - University of ChicagoJonathan W Friedberg - University of RochesterDavid W Scott - BC Cancer FoundationChristian Steidl - BC Cancer, Vancouver, British Columbia, CanadaLouis M Staudt - National Cancer InstituteLisa M Rimsza - University of Arizona
- Resource Type
- Journal article
- Publication Details
- Blood advances, Vol.9(24), pp.6443-6454
- DOI
- 10.1182/bloodadvances.2025016827
- PMID
- 40966421
- PMCID
- PMC12755980
- NLM abbreviation
- Blood Adv
- ISSN
- 2473-9537
- eISSN
- 2473-9537
- Publisher
- ELSEVIER
- Grant note
- National Cancer Institute (NCI) Specialized Program of Research Excellence (SPORE) in Lymphoma: P50-CA97274 Hope Foundation 2023 Impact AwardNCI: UH2CA292129, U10CA180888, U10CA180819
The authors acknowledge members of the Lymphoma/Leukemia Molecular Profiling Project research consortium who contributed and analyzed frozen materials for the initial Dave et al article, and some of whom also provided matched formalin-fixed, paraffin-embedded sister blocks for the migration to the nCounter platform, as well as their critical review of the assay development process. Part of the visual abstract was created using BioRender.com . Ramsower, C. (2025) https://BioRender.com /3u27sb2. This work was supported by National Cancer Institute (NCI) Specialized Program of Research Excellence (SPORE) in Lymphoma (P50-CA97274 [J.R.C.] ) ; Hope Foundation 2023 Impact Award (L.M.R.) ; and NCI awards (UH2CA292129 [L.M.R.] ; and U10CA180888 and U10CA180819 [J.W.F.] ) . The authors acknowledge their late colleague Oliver Press, the original principal investigator of the S0016 trial.
- Language
- English
- Electronic publication date
- 09/18/2025
- Date published
- 12/23/2025
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Internal Medicine
- Record Identifier
- 9984963629802771
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