NCI awards $3.46 million grant to study resistance to acute myeloid leukemia treatment

A five-year, $3.46 million grant from the National Cancer Institute recently was awarded to The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) and the University of California San Francisco (UCSF). The grant will help researchers study why some patients with acute myeloid leukemia (AML) respond to treatment while others don't. The findings could help doctors predict which patients will benefit from certain therapy before treatment even begins.

AML is a type of blood cancer that affects more than 20,000 Americans annually, most who are over age 60 and die of their disease within a short time.

Currently, a therapy called VenHMA, which combines hypomethylating agent (HMA) and the BCL2 gene-inhibitor drug known as venetoclax (Ven), is the standard care for older adults with AML. However, one third of those patients don't respond to the treatment and others relapse on therapy without a stem cell transplant.

"Better tools are needed to determine which patients are most likely to benefit from VenHMA treatment," said the grant's multiple principal investigator Uma Borate, MBBS, professor of Hematology and member of the Leukemia and Hematologic Malignancies Program at the OSUCCC – James. "Identifying biomarkers could help us make more informed treatment decisions earlier in a patient's care and uncover the causes of treatment resistance. This may lead to new therapies for patients whose leukemia returns or stops responding to treatment."

The research team will analyze blood samples obtained from an OPTI-AML clinical trial that was led by Borate. That trial was conducted at major academic medical centers in the United States and funded by Blood Cancer United to study the effectiveness of various doses of venetoclax in older adults with newly diagnosed AML.

Today, we have limited ability to predict which patients will benefit from treatment and which patients are likely to relapse,. Our goal is to identify biological signals that can guide treatment decisions and ultimately help us develop better options for patients."

Ann-Kathrin Eisfeld, MD, co-investigator, director of the Clara D. Bloomfield Center for Leukemia Outcomes Research and director for Precision Genomics Clinical Transformation, OSUCCC – James

Eisfeld is leading the large-scale bulk sequencing efforts for the project. The Ohio State team is joined by principal investigator Catherine Choy Smith, MD, of UCSF, and additional co-investigator Linde Miles, PhD, of Cincinnati Children's Hospital Medical Center.

"Ultimately, we want to move closer to a future where treatment decisions are guided by the biology of each patient's leukemia," said Borate. "That could help more patients receive the therapies most likely to work for them while accelerating the development of new options for those with resistant disease."