# Project 4: Genomic Predictors of Early Relapse in Immunochemotherapy-Treated Follicular Lymphoma

> **NIH NIH P50** · UNIVERSITY OF IOWA · 2021 · $441,654

## Abstract

ABSTRACT: Project 4. Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma and 
has a highly variable clinical course. Asymptomatic and low-tumor burden patients can initially be managed by 
observation or rituximab-monotherapy, while symptomatic and high-tumor burden patients are typically 
managed at diagnosis with immunochemotherapy (IC) as standard of care. We have shown that IC-treated FL 
patients who achieve event-free (i.e., no disease progression or re-treatment) status at 24 months after 
diagnosis (EFS24) have the subsequent life expectancy of the background age and sex matched general 
population, while those who fail to achieve EFS24 have aggressive disease with poor outcomes. One of the 
highest priorities for the new NCI-driven paradigm for progress in FL is to address early events in FL including 
understanding the underlying biology, identifying prognostic and predictive markers, and ultimately developing 
new therapeutic targets and management strategies for these patients. We hypothesize that a novel 
combination of germline (host) and somatic (tumor) genomic biomarkers, tumor gene expression, and clinical 
factors, can improve our ability to predict at diagnosis which IC-treated FL patients will have an early clinical 
failure, defined as failure to achieve EFS24. To test this hypothesis, we propose to identify, validate and 
clinically translate germline genetic biomarkers (Aim 1), somatic tumor genomic biomarkers (Aim 2), and gene 
expression signatures (Aim 3) for failure to achieve EFS24 in IC-treated FL and then develop and validate a 
novel integrative model (Aim 4) that combines clinical prognostic factors with the biomarkers identified from 
Aims 1-3. To address these aims, we have assembled an outstanding interdisciplinary team with extensive 
expertise in the proposed studies. The study leverages the established resources of the Lymphoma SPORE, 
our horizontal collaborations (LLMPP, SWOG, LYSA), and our leadership in the Lymphoma Epidemiology of 
Outcomes (LEO) cohort. Our innovative population science project will be the first to comprehensively 
discover and validate germline genetic, tumor genomic, and gene expression biomarkers for failure to achieve 
EFS24. We have designed studies that have high internal validity, with a focus on use of large patient cohorts 
with high quality biospecimens, clinical and outcome data; extensive quality control in biologic sample handling 
and assays; and multi-stage studies with external validation of results, including use of a geographically and 
racially/ethnically diverse sample of IC-treated FL patients from the LEO cohort study, which also enhances the 
generalizability of our results. Our comprehensive approach of discovery-validation and clinical translation 
should yield a reliable, multiparameter, prognostic model, with potential for major impact on the management 
of IC-treated FL patients with the ultimate goal of accurate, personalized patient ma...

## Key facts

- **NIH application ID:** 10208780
- **Project number:** 5P50CA097274-20
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** BRIAN K. LINK
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $441,654
- **Award type:** 5
- **Project period:** 2002-09-11 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10208780

## Citation

> US National Institutes of Health, RePORTER application 10208780, Project 4: Genomic Predictors of Early Relapse in Immunochemotherapy-Treated Follicular Lymphoma (5P50CA097274-20). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10208780. Licensed CC0.

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