Recurrent GBM brain tumors with few mutations respond best to immunotherapy

01/13/2021

 

The finding from a genetic analysis of tumors treated with Duke’s poliovirus therapy suggests a predictive biomarker for survival

 

Glioblastoma brain tumors are especially perplexing. Inevitably lethal, the tumors occasionally respond to new immunotherapies after the cancer returns, enabling up to 20% of patients to live well beyond predicted survival times. What causes this effect has long been the pursuit of researchers hoping to harness immunotherapies to extend more lives. 

New insights from a team led by the Preston Robert Tisch Brain Tumor Center at Duke provide potential answers. The team found that recurring glioblastoma tumors with very few mutations are far more vulnerable to immunotherapies than similar tumors with an abundance of mutations.

The finding, appearing online January 13, 2021,  in the journal Nature Communications, could serve as a predictive biomarker to help clinicians target immunotherapies to those tumors most likely to respond. It could also potentially lead to new approaches that create the conditions necessary for immunotherapies to be more effective.

“It’s been frustrating that glioblastoma is incurable and we’ve had limited progress improving survival despite many promising approaches,” said senior author David Ashley, MD, PhD, professor in the Department of Neurosurgery.  

“We’ve had some success with several different immunotherapies, including the poliovirus therapy developed at Duke,” Ashley said. “And while it’s encouraging that a subset of patients who do well when the therapies are used to treat recurrent tumors, about 80 percent of patients still die.”

Ashley and colleagues performed genomic analyses of recurrent glioblastoma tumors from patients treated at Duke with the poliovirus therapy as well as others who received so-called checkpoint inhibitors, a form of therapy that releases the immune system to attack tumors.

In both treatment groups, patients with recurrent glioblastomas whose tumors had few mutations survived longer than the patients with highly mutated tumors. This was only true, however, for patients with recurrent tumors, not for patients with newly diagnosed disease who had not yet received treatment.

 

--Duke Health News Office