Sylvester Researchers Awarded $1.5 Million Federal Grant for New Lymphoma Study

A new federal grant will support a leading-edge lymphoma research project at Sylvester Comprehensive Cancer Center, part of UHealth – University of Miami Health System.

The $1.5 million award from the U.S. Department of Defense office of the Congressionally Directed Medical Research Programs (CDMRP) will advance the collaborative work of three Sylvester lymphoma specialists.

Jonathan H. Schatz, M.D., associate professor of medicine, is principal investigator for the study, “The Role of Diffuse Large B-Cell Lymphoma Genome Complexity in Shaping Immune Responses to Anti-CD19 Chimeric Antigen Receptor T-Cell Therapies.” The study will focus on identifying drivers of resistance for patients whose diffuse large B-cell lymphomas (DLBCLs) did not respond to initial chemotherapy or suffered a relapse after treatment.

Dr. Schatz said an immunotherapy called CAR-19 (CD19 chimeric antigen receptor T-cell therapy) generates a positive response in 30-40% of these patients and could potentially be more effective if delivered in combination with other drugs.

“Currently, there are no clear biomarkers for selecting the CAR-19 therapy rather than established second-line chemotherapy followed by stem cell transplants,” said Dr. Schatz. “We also want to learn more about the factors driving resistance in the more than 60% of DLBCL patients who do not respond to CAR-19.”

In the Sylvester study, Dr. Schatz and his co-investigators Francesco Maura, M.D., assistant professor of medicine, and Juan Alderuccio, M.D., associate professor of medicine, will assess tissue samples from more than 60 CAR-19-relapsed patients for genomic biomarkers — the largest such study to date.

“We recently showed that characteristics of tumor genomes detectable by whole-genome sequencing can predict the likelihood of failed CAR-19 responses more strongly that previously reported markers,” Dr. Schatz said. “We will leverage these findings by studying hundreds of additional cases and determine mechanisms in laboratory models.”

Looking ahead, he said, “Our long-term goal is to fuel development of more effective genomic biomarker-driven immunotherapies by revealing detailed resistance mechanisms. Resolving these gaps in knowledge will provide new routes to improve relapsed or refractory patient outcomes through rational choices among the growing menu of options.”

Tags: B-cell lymphomas, CAR-19, Congressionally Directed Medical Research Programs, Department of Medicine, diffuse large B cell lymphoma, Dr. Francesco Maura, Dr. Jonathan H. Schatz, Dr. Juan Pablo Alderuccio, lymphoma, Sylvester Comprehensive Cancer Center, U.S. Department of Defense