Immunotherapy has unleashed a revolution in care for some cancer patients. But most immunotherapies help only a small subset of patients, meaning doctors often have to resort to a trial-and-error process to determine who might actually benefit from the novel treatments.
Now, scientists have developed a new metric they believe can help predict whether patients will respond to a class of immunotherapies known as checkpoint inhibitors, drugs that train the body’s natural defenses on cancer cells.
The metric, produced by scientists at the University of Texas Southwestern Medical Center and described in a new paper published Friday in the journal Science Immunology, focuses on neoantigens — molecules on the surface of cancer cells that are foreign to the immune system.
Scientists have long assumed that the more neoantigens a patient’s cancer has, the more likely that immunotherapy will work. But the new metric takes a different tack, looking at the specific genetic profiles of each neoantigen to sort out which ones might bode well for treatment.
These profiles are central to determining the responsiveness of patients to immunotherapy, according to the study. And the metric these scientists have invented, dubbed the Cauchy-Schwarz index of Neoantigens (CSiN), is far broader than any metric that has linked immunotherapy response to neoantigens in the past, according to Tianshi Lu, an author of the study, which was funded by the National Institutes of Health, the Cancer Prevention Research Institute of Texas, and American Cancer Society.
“A lot of patients will benefit from our findings about responsiveness to immunotherapy because it is very popular among cancer patients and, as a form of treatment, it is more specific to tumor cells,” said Lu.
In the study, Lu and her colleagues analyzed clinical responses to immunotherapy in 501 treated patients with cancer, while using the overall survival of 1,978 patients with cancer as baseline. The results demonstrated that patients with better responses to immunotherapy are more likely to have a higher score based on the new metric than patients with worse responses. Additionally, patients with sustained response are more likely to have higher scores than patients with short-term progression.
James Gulley, the director of Medical Oncology Service at National Cancer Institute, said the new score is “one clue” that could help determine who may respond to immunotherapies and who may not. But that doesn’t make it a cure-all.
“We need additional prospective studies and clues from multiple different sources to really narrow down the list of suspects or, in this case, who’s going to respond [to immunotherapy],” said Gulley, who was not involved in the study.
The incorporation of RNA signatures and protein signatures with CSiN, in future studies, might improve the predictive and prognostic ability of the metric, according to Gulley.
Vinay Prasad, a hematologist-oncologist and associate professor of medicine at Oregon Health and Science University, suggested the success of immunotherapies for some patients has led to a level of public misunderstanding about their effectiveness.
“Even in cancers where immunotherapy has no FDA approvals, patients ask for it, in part because they’ve heard about it on the news or TV.
“But,” he said, “we have also seen many patients for whom immunotherapy has caused devastating side effects.”
Those side effects — the result of turbocharging T cells and revving up the immune system — can include severe fevers, extreme fatigue, low blood pressure, and organ swelling, among others.
Prasad, asked about the new study, suggested CSiN still risks offering patients a false sense of hope.
“Is this so good a test … that there’s zero percent chance of immunotherapy benefiting you?” he said. “It doesn’t look like this test has that level of discrimination.”
While Prasad thinks trying to link neoantigen profiles to responsiveness to immunotherapy treatment is a “worthy goal,” he also said “we are miles and miles away” from reaching it.