Blood Test Predicts Patient Response to Immunotherapy

The blood-based liquid biopsy can be used as a relatively noninvasive diagnostic tool to detect onset of disease, monitor its progression, and measure its retreat.

In the study, 45% of patients with over 3 genomic mutations (of unknown significance) in ctDNA responded to CII. The patients-group with fewer alterations had a 15% response rate.

"CII is exciting, but it is currently given to patients with all types of cancer, and most of the time it is not known if it will result in a response," said senior-author Razelle Kurzrock, MD, of UCSD School of Medicine, "Indeed, more than 80% of patients with cancer fail to respond to CII."

Patients with a high number of mutations also had longer progression-free survival. Those who responded to CII (at 2 months) and had high numbers of ctDNA genomic mutations had a median response lasting nearly 2 years. "Considering that many of these patients had advanced disease that was resistant to many other therapies, this result is impressive," said Dr. Kurzrock.

Once reactivated with the use of CII, the immune system needs to recognize the cancer cells. The more mutations a cancer cell harbors, the more it stands out compared to normal tissue, and the easier it is for the immune system to recognize and target a tumor. "Tumors that have the most mutations, and used to be considered the worst tumors, are now considered the best cancers in that they are the most amenable to treatment with immunotherapy," said Dr. Kurzrock.

The team lead by Dr. Kurzrock and Dr. Khagi analyzed results from the Guardant360 assay for ~ 70 genes for genomic alterations in blood-derived DNA – from 69 patients with different types of cancers who were treated with checkpoint inhibitors (CI). "We can take a simple blood sample, which is less painful, less expensive, and can be repeated to determine who is at an increased chance of response to immunotherapy," said Dr. Kurzrock. "This technology opens up a whole new approach to immunotherapy."

The authors suggest larger studies are needed to corroborate if blood-based liquid biopsy can be effectively used to assay for biomarkers of response to CII across a variety of cancers. Dr. Kurzrock and colleagues are already using liquid biopsy technology in the Profile Related Evidence Determining Individualized Cancer Therapy (PREDICT) clinical trial -- a project focusing on the outcome of patients who have genomic testing performed on their tumors and are treated with targeted therapy.

The study, by Khagi Y et al, was published October 1, 2017, in the journal Clinical Cancer Research.

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University of California San Diego School of Medicine