Recurrent Glioblastoma Brain Tumors With Fewer Mutations Respond Better to Immunotherapy

The treatment of glioblastoma brain tumors has remained a significant challenge, as some tumors respond to new immunotherapies after they've grown back, whereas others do not. Although the tumors often do lead to mortality, 20% of patients live beyond predicted survival times. For this reason, many researchers have investigated what causes some patients’ tumors to respond to immunotherapies so that they could pinpoint how to treat others more effectively.

A recent study by Duke's Preston Robert Tisch Brain Tumor Center added to this body of research on glioblastoma, finding that recurring glioblastoma tumors with very few mutations respond significantly better to immunotherapies than similar tumors with multiple mutations.

The results of the study may help clinicians target immunotherapies directly at tumors with the highest likelihood of responding to the treatment, which may also allow for the discovery of new approaches to improving the efficacy of other immunotherapies as well, according to the authors.

"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 departments of Neurosurgery, Medicine, Pediatrics and Pathology at Duke University School of Medicine (Duke), in a press release. "We've had some success with several different immunotherapies, including the poliovirus therapy developed at Duke. And while it's encouraging that a subset of patients who do well when the therapies are used to treat recurrent tumors, about 80% of patients still die."

The researchers conducted genomic analyses of recurrent glioblastoma tumors from patients who had been treated at Duke with the poliovirus therapy, as well as others who had received checkpoint inhibitors.

Among both treatment groups, the researchers observed that the patients with recurrent glioblastoma tumors with fewer mutations survived longer than patients with tumors with more mutations. However, they also found that this was specific to patients with recurrent tumors, as the same pattern did not occur among patients with newly diagnosed disease who had not received prior treatment.

"This suggests that chemotherapy, which is the standard of care for newly diagnosed glioblastoma, might be altering the inflammatory response in these tumors," Ashley said in the press release.

He also noted that chemotherapy may be acting as a primer that triggers the development of an inflammation process in recurrent tumors. Ashley added that the results from this study may be applicable to other types of tumors than glioblastoma, such as kidney and pancreatic cancers. Both of these cancer types present with similar correlations between low tumor mutations and improved response to immunotherapies.

REFERENCE

Recurrent GBM brain tumors with few mutations respond best to immunotherapy. Durham, NC: Duke University School of Medicine; January 13, 2021. https://www.eurekalert.org/pub_releases/2021-01/dumc-rgb011121.php. Accessed January 19, 2021.