Translating molecular profiles into treatment approaches to target disparities in lymphoma
Jean Koff
MD, MScWinship Cancer Institute
Project Term: October 1, 2024 - September 30, 2029
Although many patients with diffuse large B-cell lymphoma (DLBCL) are cured with standard therapy, others will die from their disease. Survival is significantly worse for African American (AA) patients and those with Epstein- Barr virus (EBV), which is common in patients from Latin America. The reasons behind these poor outcomes are not well understood, in part because most studies of molecular features in lymphomas have not included enough patients from these racial and ethnic groups.
Lymphoma tumors include not just the cancer cells themselves, but also surrounding cells and proteins that help the cancer cells survive. To understand why AA DLBCL patients and those with EBV have worse outcomes, we will look at differences in genes and tumor make-up in a large collection of DLBCL samples with good representation of these patient groups. Our goal is to find the factors most important to target with new treatments to improve survival for AA and EBV+ patients. We will also build innovative models of DLBCL in the lab to (1) discover how tumor make-up and gene changes affect tumors’ response to treatment, and (2) test new therapies designed to benefit AA DLBCL patients and patients with EBV-associated DLBCL.
Overall, our LLS SCOR Program seeks to bridge the knowledge gap in molecular features of DLBCL in underrepresented populations, and fast-track development of novel targeted therapies that can improve outcomes for these vulnerable patients.
Diffuse large B-cell lymphoma (DLBCL) is the most common blood cancer. Most patients with DLBCL are cured with standard treatment, but some people die from DLBCL if their disease does not respond to treatment, or comes back later after responding at first. Survival is significantly worse for African American (AA) patients and those with Epstein-Barr virus (EBV), which is common in patients from Latin America. Unfortunately, the reasons behind the poor outcomes in these patient groups are not well understood. In large part, this is because most of the studies looking at genes and other molecular features that cause lymphomas to be resistant to treatment have not included enough patients with African, Hispanic, and Native Indigenous ancestry. It is important to consider that tumors include not just the cancer cells themselves, but also surrounding cells and proteins that give the tumor its structure and help the cancer cells survive. To understand why AA DLBCL patients and those with EBV have worse outcomes, we will look at differences in genes and tumor make-up in a large collection of DLBCL patient samples with good representation of these patient groups. Our goal is to find which factors are most important to target with new treatment strategies in order to improve survival for AA and EBV+ patients. We will also build innovative models of DLBCL tumors in the lab to discover how tumor make-up and gene changes affect whether the tumor responds to treatment. We will use these models to test new therapies designed specifically to benefit AA DLBCL patients and patients with EBV-associated DLBCL.
Overall, our LLS SCOR Program seeks to bridge the knowledge gap in molecular features of DLBCL in underrepresented populations, and fast-track development of novel targeted therapies that can lead to better outcomes for these vulnerable patients. To achieve these aims, our four-site coalition involving Emory University, MD Anderson Cancer Center, Weill Cornell Medicine, and Georgia Institute of Technology will leverage our access to large DLBCL patient sample databases, our expertise in cutting-edge exploration of lymphoma biology, and our significant experience translating lab findings into new treatment approaches that can then be tested in clinical trials. Our team of investigators already engage in fruitful inter-institutional collaborations with each other and share a dedication to our ultimate goal: eliminating health disparities for lymphoma patients.