# Genetic Predictors of Early Clinical Failure in Diffuse Large B Cell Lymphoma

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2021 · $657,422

## Abstract

PROJECT SUMMARY/ABSTRACT
Diffuse large B cell lymphoma (DLBCL) compromises nearly 40% of all newly diagnosed non-Hodgkin
lymphomas (NHL) in the U.S. Currently, mainly clinical factors are used to identify high versus low
risk patients and to predict overall survival, but with modest utility. We have recently shown that
newly diagnosed patients treated with anthracycline-based immunochemotherapy (standard of care)
who do not have disease progression or relapse, retreatment, or death within 24 months of diagnosis
(termed event-free survival or EFS24) for DLBCL have a normal life expectancy, while patients who
fail to achieve this sentinel landmark have very poor outcomes. While we have identified clinical
predictors of these endpoints, we hypothesize that both somatic (tumor) and germline (host) genetic
biomarkers can improve our ability to predict at diagnosis which patients will have an early clinical
failure and help identify novel biology and therapeutic approaches. Our preliminary data from whole-
exome sequencing and genome-wide association studies in DLBCL patients suggests that there are
both somatic and germline genetic biomarkers that predict failure to achieve EFS24, and that these
are different from known drivers and susceptibility loci. Building on these findings, we propose the
following specific aims are: 1) To identify, validate and clinically translate somatic genetic biomarkers
for failure to achieve EFS24; 2) To identify, validate, and clinically translate germline genetic
biomarkers for failure to achieve EFS24; and 3) To develop and validate an integrative model that
combines somatic and germline genetic biomarkers with clinical prognostic factors. For each aim, we
will also initially assess biomarker function through the use of bioinformatics tools, and when
applicable, with initial laboratory interrogation in model systems. We will address our aims using the
established and extensive resources of the Mayo Clinic and University of Iowa Lymphoma
Specialized Program of Research Excellence (SPORE) and Lymphoma Epidemiology of Outcomes
(LEO) cohort, and established collaborations with the LYSA (French Lymphoma Trials Group) and the
Mayo Clinic Department of Laboratory Medicine and Pathology. We anticipate that our results will
have a major impact on the management of DLBCL by leading to clinical translation of both host and
tumor genetic biomarkers for risk stratification, identifying high-risk patients who might benefit from
more intensive therapies or non-standard first-line drug regimens, and identification of novel biology
and therapeutic targets.

## Key facts

- **NIH application ID:** 10219978
- **Project number:** 5R01CA212162-05
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** JAMES R CERHAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $657,422
- **Award type:** 5
- **Project period:** 2017-08-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10219978

## Citation

> US National Institutes of Health, RePORTER application 10219978, Genetic Predictors of Early Clinical Failure in Diffuse Large B Cell Lymphoma (5R01CA212162-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10219978. Licensed CC0.

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