Optimizing Genetic Testing Remains Challenge in Hematologic Malignancies

The scope of genetic testing continues to evolve, yet in hematologic malignancies, Andrew Laramore, MD, says that it is difficult to determine which patients should be tested and how panels should be best utilized.

“Nobody has a clear-cut answer as to whether everybody should get tested, or whether it should be done on a case-by-case basis, said Laramore, a pathologist at Diagnostic Pathology Services.

While genetic tests on patients with chronic myeloid leukemia (CML) may be positive for BCR-ABL1, a molecular driver for the disease, there are other mutations that may show up on panels in which practitioners are unsure if they are related to the disease or not, he added.

OncLive: What are some advancements that have occurred in the pathology of hematologic malignancies in the past few years?

Does everyone receive genetic testing? How do you determine who receives it?

Depending on the type of malignancy, what are some of the more common genes that are tested for?

In an interview during the 2018 OncLive^® State of the Science Summit^TM on Hematologic Malignancies, Laramore focused on the evolution of genetic testing in hematologic cancers and optimal methods of detection.Laramore: One of the most interesting areas of pathology, specifically hematopathology, is the advancement in genetic testing. We're now able to do very sophisticated and thorough genetic testing at increasingly decreased costs. The question that most oncologists and even pathologists have from a diagnostic standpoint is how best to use these tools, and how to utilize the data that these tools provide.That's the conundrum. It all depends on a multitude of factors from an individual, community, and population standpoint; these are all important perspectives to consider when deciding how to use these tests. In some circumstances, it’s very expensive testing, and not everybody has access to it. Because not every group’s algorithmic approach is the same, it can be very challenging to know what the standard should be. Many of the panels we are working with now can test anywhere from 3 to 600 “hotspots,” as they call them. While these panels can be done quickly and inexpensively, we are inundated with these data, and the significance of the information doesn’t necessarily translate upfront. That’s definitely a challenge. It's almost like you're putting the cart in front of the horse, in some circumstances.

Can you share more insight on these “hotspots” you described?

Do family members of patients also undergo genetic testing?

How do you see genetic testing evolving in hematologic malignancies?

What is an important factor in proceeding with testing?

In CML, we can do BCR-ABL1 fluorescence in situ hybridization testing. If it comes back positive, that's a pretty clear-cut scenario. However, in many instances, mostly in myeloid dysplasia workups, we'll get mutations that we’re unsure if they're related to disease, or if they're just part of the normal aging process. [At this meeting] we specifically discussed the role of next-generation sequencing in the diagnosis of myeloid disorders—particularly neurologic deficit scores. There are 600 genes, so [hotspots] are on that list because we think they have significance. We don't know exactly what they are, but we know they are probably significant in some way.That raises an interesting but somewhat different point regarding hereditary cancer syndromes, and that is a very hot medical ethics area right now. I don't have to deal with that aspect of it so much. We are mostly using these tools as indicators of somatic mutations in neoplasms, whereas they can alternatively convey significance to whole families. If you have this mutation, you may end up with brain cancer—so do you want to know? Do you want insurance companies to know that sort of thing? It utilizes the same methodologies that we're working with, but in a different sense.What we are seeing now is the production of proprietary benchtop laboratory devices that can run at a lower cost to the patient with the same amount of information. My prediction is that as time goes on, the cost of these tests will go down and make them more accessible to patients. In the same timeframe, I believe we will become more familiar with the information and how best to utilize it. Don't order the tests unless you know what you're going to do with the information. That's the one problem with the reflex testing in algorithmic approaches; sometimes you have to stop and think about it.