DNA mutations shed in blood predicts response to immunotherapy in patients with cancer

October 2, 2017

In a first-of-its-kind study, University of California San Diego School of Medicine researchers report that a blood sample, or liquid biopsy, can reveal which patients will respond to checkpoint inhibitor-based immunotherapies.

"We can help predict response to immunotherapy by measuring the number of mutations in circulating tumor DNA using a simple blood test," said Yulian Khagi, MD, UC San Diego Moores Cancer Center fellow and first author. "Immunotherapy can result in serious side effects, and therefore being able to predict who will respond is important to mitigating potential risk to each patient."

The findings, publishing in the journal Clinical Cancer Research on Oct. 2, show that 45 percent of patients with more than three genomic alterations (specifically, variants of unknown significance) detected in the tumor DNA that circulates in the bloodstream—known as ctDNA—responded to checkpoint inhibitor-based immunotherapy. Patients with fewer alterations had a 15 percent response.

"Checkpoint inhibitor immunotherapy 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 Razelle Kurzrock, MD, director of the Center for Personalized Cancer Therapy at UC San Diego Moores Cancer Center and senior author of the study. "Indeed, more than 80 percent of patients with cancer fail to respond to checkpoint inhibitor immunotherapy."

Patients with a high number of alterations also had longer progression free survival, or the period of time in which a patient lives with cancer without it advancing. Those who responded to immunotherapy at two months and had high numbers of genomic alterations in the blood had a median response last nearly two years.

"Considering that many of these patients had advanced disease that was resistant to many other therapies, this result is impressive," said Kurzrock.

Study findings mirror what has been previously described in genomic testing of tissue samples. However, in this report, the result was obtained from a small tube of blood without a tissue biopsy.

Once reactivated with the use of checkpoint inhibitor immunotherapy, the immune system needs to recognize 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 Kurzrock.

In this analysis, the team lead by Kurzrock and Khagi analyzed blood-derived DNA from 69 patients with different types of cancers who were treated with checkpoint inhibitors. They used the Guardant360 assay, a comprehensive liquid biopsy which evaluated up to 70 genes for genomic alterations.

"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 Kurzrock. "This technology opens up a whole new approach to immunotherapy."

A liquid biopsy is a diagnostic tool based on the idea that critical genetic information about the state of disease can be found in blood or other fluids. One vial of blood could be used to detect the onset of disease, monitor its progression and measure its retreat less invasively than a tissue biopsy.

Kurzrock is 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 authors suggest larger studies are needed to corroborate that blood-based liquid biopsy can be used as a viable, noninvasive, predictive biomarker for response to checkpoint inhibitor-based immunotherapy across a variety of cancer.

Explore further: Liquid biopsies find distinct genomic profiles in most patients with carcinoma of unknown primary

Related Stories

Liquid biopsies find distinct genomic profiles in most patients with carcinoma of unknown primary

August 15, 2017
Bottom Line: Next-generation sequencing of circulating tumor DNA (ctDNA) identified distinct genomic profiles with potentially targetable alterations in 99.7 percent of patients with carcinoma of unknown primary (CUP) who ...

FDG-PET/CT predicts melanoma patients' response to immune checkpoint inhibitor therapy

September 5, 2017
Advanced melanoma, a type of skin cancer that has spread to other areas of the body, has a poor prognosis, but immune checkpoint inhibitor therapy can be effective for some patients. Research highlighted in the featured article ...

Drug combination may improve impact of immunotherapy in head and neck cancer

September 21, 2017
Checkpoint inhibitor-based immunotherapy has been shown to be very effective in recurrent and metastatic head and neck cancer but only in a minority of patients. University of California San Diego School of Medicine researchers ...

Cancer immunotherapy may get a boost by disabling specific T cells

September 7, 2017
Cancer immunotherapy drugs only work for a minority of patients, but a generic drug now used to increase blood flow may be able to improve those odds, a study by Columbia University Medical Center (CUMC) researchers suggests.

New immunotherapy combination shows promise for patients with advanced melanoma

April 5, 2017
Treatment with a combination of ipilimumab (Yervoy) and Coxsackievirus A21 (CVA21; Cavatak) led to durable responses in a number of patients with advanced melanoma, including some whose melanoma had progressed despite prior ...

The big question: Will cancer immune therapy work for me?

September 20, 2017
Dennis Lyon was a genetic train wreck. Cancer was ravaging his liver, lungs, bones and brain, and tests showed so many tumor mutations that drugs targeting one or two wouldn't do much good. It seemed like very bad news, yet ...

Recommended for you

Study shows how nerves drive prostate cancer

October 19, 2017
In a study in today's issue of Science, researchers at Albert Einstein College of Medicine, part of Montefiore Medicine, report that certain nerves sustain prostate cancer growth by triggering a switch that causes tumor vessels ...

Gene circuit switches on inside cancer cells, triggers immune attack

October 19, 2017
Researchers at MIT have developed a synthetic gene circuit that triggers the body's immune system to attack cancers when it detects signs of the disease.

One to 10 mutations are needed to drive cancer, scientists find

October 19, 2017
For the first time, scientists have provided unbiased estimates of the number of mutations needed for cancers to develop, in a study of more than 7,500 tumours across 29 cancer types. Researchers from the Wellcome Trust Sanger ...

Suicide molecules kill any cancer cell

October 19, 2017
Small RNA molecules originally developed as a tool to study gene function trigger a mechanism hidden in every cell that forces the cell to commit suicide, reports a new Northwestern Medicine study, the first to identify molecules ...

Researchers target undruggable cancers

October 19, 2017
A new approach to targeting key cancer-linked proteins, thought to be 'undruggable," has been discovered through an alliance between industry and academia.

Fundamental research enhances understanding of major cancer gene

October 19, 2017
New research represents a promising step towards better understanding of a key cancer gene. A long-running collaboration between researchers at the Babraham Institute, Cambridge and the AstraZeneca IMED Biotech Unit reveals ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.