This story has been corrected regarding the type of transplants used in AML and the use of sequencing in myelodysplastic syndrome.
NEW YORK – NeoGenomics this month launched a new next-generation sequencing panel called AML Express, which covers a handful of gene alterations with prognostic and predictive value for the care of patients with acute myeloid leukemia. The test also promises a turnaround time of as little as three days, which the company and clinicians believe is crucial for this population.
Genomic testing for hematologic cancers has been available for more than a decade, but AML has specific features that NeoGenomics argued make broader tests, which take longer to read out, less desirable to physicians.
"All cancer diagnoses are disruptive … but for a patient who gets a new diagnosis of acute myeloid leukemia, it's really a cataclysmic experience," said Nathan Montgomery, NeoGenomics' VP of medical services.
"This is a patient who might have been reasonably well a couple of weeks ago. … They present to the hospital … and when they get that diagnosis, life changes immediately. … You don't go home and get your stuff. You get admitted immediately, and now you're in the hospital for more than 30 days."
AML patients, Montgomery said, especially young individuals, are put on what is called induction chemotherapy, an "incredibly aggressive" course, which renders them vulnerable, with essentially no functioning immune system.
According to Montgomery, the introduction of targeted therapies has not meaningfully replaced that first induction step, as such drugs have done for some solid tumors, but it does let oncologists "layer on some more precision" to what they're doing.
"The challenge is that the patient is so sick they can't wait 10 days or 12 days for a result to come back with the critical information," he said. "In addition, because they're in the hospital, they're accumulating the cost of the hospital stay."
Although discussion of cost savings is ubiquitous in the diagnostics development world, Montgomery said that AML presents an opportunity to make an especially straightforward case. "Fewer days in a hospital is less cost to a patient and to the health system," he said.
According to Montgomery, there are several ways that heme-oncologists use genomic information in AML that may differ from some of the predominant precision medicine paradigms in other cancer types.
For one, AML is a notably heterogeneous disease. "The current World Health Organization classification is very driven by genomic findings, so payors are going to be paying for a test in that regard, but you really also have to get enough information beyond therapy selection so that you are also classifying [a patient's risk] with appropriate granularity," Montgomery said.
"In AML, risk stratification isn't just prognostic information about how much time you might have. It is actually driving critical therapy decisions," including whether a patient receives an allogenic bone marrow transplant or one from a donor, Montgomery said.
"Transplant itself is associated with such high mortality that you have to have some information," he further noted. "Even if you get through the initial period, and you get the patient to the right therapy, and you get them into remission, you have to have a pretty clear sense of their relapse risk."
From his perspective, Montgomery said, the design of the NeoGenomics panel reflects a recognition of the need for that risk prediction and an embrace of guideline-recognized markers to guide specific targeted therapies while still allowing for a rapid test.
"We're probably not digging in as deep as you would in a broad platform panel that didn't require rapid turnaround, but … we want to make sure that we have appropriate content, so that you can risk-stratify that patient with necessary granularity for those downstream decisions," he said.
Montgomery said that the need for panel testing, rather than single-gene tests, has become well cemented in the AML treatment community, based on a realization that disease classification relies on multiple markers, as does risk assessment.
Although there are trade-offs, Montgomery said that he believes a moderately sized panel with rapid turnaround time is "quite advantageous" for a newly diagnosed AML patient.
NeoGenomics isn't alone in recognizing this need, Montgomery added. Medical centers are increasingly implementing rapid panels in-house. But not all health systems or providers have the ability or resources to perform next-generation sequencing, which makes a send-out option crucial for equitable access.
David Swoboda, a hematologist-oncologist at Tampa General Hospital, said that although trends have been for hospitals to bring certain NGS testing in-house, it can be hard to keep up with an evolving biomarker landscape. This led him and his colleagues to outsource their AML analysis.
"Across heme malignancies, AML and myelodysplastic syndrome are the farthest along in using targeted sequencing. And the reason … is because we have the targeted agents. We have IDH1, IDH2 inhibitors. We have drugs approved for FLT3 mutations, and we have certain drugs that we add on to chemotherapy for certain subsets of patients. Pfizer's Mylotarg is one, and the other would be venetoclax," Swoboda said.
A trial called Beat AML successfully demonstrated that patients treated based on genomic information had better survival compared to those who were not, he noted.
There are also a new class of targeted drugs called menin inhibitors that Swoboda said are likely to enter the market, led by Syndax's revumenib, which he said he and his colleagues expect to receive US Food and Drug Administration approval in the next couple of months.
"There are probably six other agents in clinical trials, so targeted sequencing in AML is not really going away," he said.
Despite this, hematologic cancers have not seen the establishment of dedicated, FDA-recognized companion diagnostic indications in the way that solid tumors have.
Montgomery said that this likely reflects the fact that the main utility of sequencing in the heme space is not necessarily for therapy selection but more so for classification and risk stratification.
"AML is a genomically diverse disease, so even the most common alterations that would be targetable are going to be a smaller slice of a larger pie. … It's also a less common disease, and so there are, realistically, probably also different economic incentives at play in driving investment for true companion diagnostics," he added.