Further Evaluating Biomarkers May Help to Better Interpret Which Patients Are Eligible For Immunotherapy

Getting rid of the "blanket statement" and looking deeper into genetics may allow patients with cancer who are older than 60 years to become eligible for immunotherapy, highlighting the importance of further research on the topic.

Patients with cancer who are older than 60 years should still be evaluated for biomarkers, as well as characteristics like frailty and age, when it comes to immunotherapy eligibility, according to results from a recent study. Data from the study highlights the need of deeper research into patient genetics.

“The story that I would love to get across is the value of patient research and the value of patient genetics, and how data really helps to drive new discoveries of the biology,” Elana Fertig, director of the Division of Biostatistics and Bioinformatics and Research, Program in Quantitative Sciences, associate cancer center director of qualitative sciences and associate professor of oncology, biomedical engineering and applied mathematics and statistics at Johns Hopkins University in Baltimore, Maryland, explained in an interview with CURE®. “I think in terms of immunotherapy, what our data would suggest is that we should be evaluating immunotherapy biomarkers, as well as patient characteristics, like frailty and things like that to be sort of making an offset, and not just making a blanket statement (like) somebody is over this age, they shouldn't be getting immunotherapy. Some of those biomarkers might still be relevant.”

These findings may affect nearly two thirds of all new cancer diagnoses, which is the estimated number of cancer cases in patients older than 60 years, according to the Centers for Disease Control and Prevention.

In the study, Fertig, who was co-leader on the study and holds a PhD in applied mathematics and scientific computing, and fellow researchers examined data from a public database to evaluate the genomics, tumors and healthy tissues and how these factors can be impacted by aging.

From these data, researchers reported that aging is associated with factors like an increased number of mutations in tumor cells, increased expression of immune checkpoint proteins and increased interferon gamma signaling, as well as decreased immune response, lack of diversity of T cell receptors and an increased number of immune suppressing cells.

“In the normal aging process, it's known that a lot of immune suppressive mechanisms occur that make the immune system less functional just due to the natural aging process. And what this study found was, contrary to our expectation, a lot of the biology of things that we would expect to be immunosuppressive, we didn't observe as much in the tumor as we would have expected. And so we observed across age, a more activated immune landscape than we would have expected just going in based on the normal aging process,” Fertig, who is also co-director at the Convergence Institute at John’s Hopkins University, added.

These findings highlight the need to further investigate the impact of genetic biomarkers, according to Fertig, as well as the importance of clinical research and access to public data.

Next steps, according to Fertig, would be to start a larger study that looks specifically at older patients who are being considered for immunotherapy. “In my ideal study, what I would want to see is patients who are being considered for immunotherapy, specifically in the older age group, who have the appropriate health characteristics to get it, where you see these sort of precision trials that are driven-based on molecular biomarkers or cellular biomarkers of immunotherapy population, and then having those data if they could be reported back so that we can really evaluate how the biology changes specifically in the context of therapy would be incredibly valuable,” she concluded.

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