Biomarkers Still Critical Challenge in Immunotherapy

Janice M. Mehnert, MD

Janice M. Mehnert, MD

The search for effective biomarkers is still one of the biggest challenges in cancer, particularly in immunotherapy, said Janice M. Mehnert, MD.

In an interview withTargeted Oncology, Mehnert, Rutgers Cancer Institute of New Jersey, discusses the wide variety of biomarkers that may occur from patient to patient, as well as from tumor type to tumor type. Mehnert also specifically touches on PD-L1 expression, and how the "jury is not out" on the testing being helpful when choosing a treatment.

TARGETED ONCOLOGY:In your article in the 2016 ASCO Educational Book, you describe biomarkers as "a crucial missing link in translating immunotherapy into clinical practice." Could you elaborate on that?

Mehnert:

I think that we've all agreed that identifying biomarkers that will predict which patients will respond to therapy, as well as which patients may have toxicity, is critical. Part of the challenge is that the immune system is very dynamic, and so it's not quite as clear-cut as some of our discovered genomics tests, where it’s possible to do PCR and find a mutation, and really have a clean line between target and treatment. This is much, much more complicated, and that's part of what I'm alluding to when I say that.

TARGETED ONCOLOGY:Can you recap your recent talk on immune biomarkers?

Mehnert:

I talked about immune biomarkers and how they fit into different categories. There are biomarkers that are soluble and cellular, there are biomarkers that are specific to the tumor itself, and then there are biomarkers that are specific to the host. In doing that, we'll take a brief whirlwind tour through the retrospective analyses that have been out there, as well as take a look at what's going on in terms of genomics and in terms of helping us to identify things like mutation load and tumor infiltrating lymphocytes that are really going to be a part of the future in terms of trying to figure out which patients will respond to immunotherapy.

TARGETED ONCOLOGY:From a scientific standpoint, why do you think it's so challenging to identify biomarkers for immunotherapy?

Mehnert:

It's part of what we just touched on. The immune system is in constant flux, and in a situation like that, everybody's immune response is different. The response that is kicked into action by these checkpoint inhibitors is going to vary from patient to patient, and it also varies from disease to disease. Part of the problem is a little bit of being a victim of our own success, in that we have a drug now that actually has activity in so many different tumor types, which is sort of an unprecedented paradigm in oncology.

That being said, it's not the same in all of those tumor types. We heard at ASCO that even toxicity may be different from disease type to disease type in a small-cell lung presentation. It was mentioned that maybe the doses won't even be the same among diseases. That's not something we're used to, so I think that's going to be part of what we need to learn.

TARGETED ONCOLOGY:What immunotherapy biomarkers look promising, and in which tumor types?

Mehnert:

Across the fields, we agree that PD-L1 expression is important. It's likely to enrich for the probability of the response, but it is far from perfect. Assays are not standardized across companies, across tumor types, and it's not even clear that in certain tumor types it will matter as much as in other tumor types. For instance in melanoma, we don't check PD-L1 expression routinely before we prescribe immunotherapy. So I think it'll be important, but by no means do I think it's the answer.

I am very interested in hearing more about how to measure tumor mutation load. There were several recent presentations that even discuss using next-generation sequencing as a surrogate for whole exome sequencing to identify extreme cases of high mutational load, and that may be predictive. That needs further validation, but I think it's very interesting.

TARGETED ONCOLOGY:What is important for practicing oncologists to know about immune therapy biomarkers at this point?

Mehnert: