Researchers at University Hospital of the Ludwig-Maximilians-University Munich are working towards creating a prognostic model for lymphoma patients based on the presence of genetic mutations in patient DNA. The model, called m7-FLIPI by the researchers, uses seven genes known to be associated with lymphoma to assign patients to a risk level for treatment failure.
“Integration of the mutational status of seven genes with clinical risk factors improves prognostication for patients with follicular lymphoma receiving first-line immunochemotherapy and is a promising approach to identify the subset at highest risk of treatment failure,” wrote the authors in their study, “Integration of Gene Mutations in Risk Prognostication for Patients Receiving First-line Immunochemotherapy for Follicular Lymphoma: A Retrospective Analysis of a Prospective Clinical Trial and Validation in a Population-Based Registry,” which was published in The Lancet Oncology.
Before this study, scientists knew there were genes associated with worse outcomes in follicular lymphoma. However, other studies did not look at more than one gene at a time, losing the potential of identifying multiple risk factors for non-response to treatment. It is particularly important to be cognizant of which patients carry certain mutations and what type of response those patients have during treatments, such as the now-commonly-prescribed rituximab.
Accordingly, researchers looked at data available from the Phase 3 trial GLSG2000, in which patients were treated with immunochemotherapy consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Biological samples were all taken before the start of the study. The researchers then used DNA deep sequencing to find mutations in patient DNA.
In total, seven genes were included in the model: EZH2, ARID1A, MEF2B, EP300, FOXO1, CREBBP, and CARD11. Mutations in this group of genes were able to stratify patients into low or high risk, as defined by the five-year failure-free survival rate. High risk patients were most likely to have a poor outcome during treatment.
“If validated in subsequent studies, the m7-FLIPI could be highly significant for the medical community, as high-risk patients are clearly underserved by current standard treatment and should be prioritized for innovative treatment options,” wrote the authors. Knowing a patient’s genetic signature could therefore be important to predict the chance of survival if a certain treatment regimen is recommended.