NEW YORK – Lab leaders have been noting a growing embrace of comprehensive sequencing tests to aid the diagnosis and care of hematologic cancer patients.
Although blood cancers were some of the first malignancies found to harbor clinically actionable genetic changes, solid tumors, like lung or breast cancers, have captured much more attention in the advance of precision medicine over the last decade.
Despite this, pathologists and other stakeholders said at the Association for Molecular Pathology annual meeting last week that the value of comprehensive genomic profiling — as opposed to narrower panels or single-gene biomarker tests — is gaining in hematology-oncology. At the same time, adoption remains uneven and reimbursement uncertain, especially among commercial payors.
"We and many oncologists, especially academic oncologists, view this idea of comprehensive genomic profiling as the gold standard in terms of precision medicine right now. It makes more sense to just run a big broad assay to maximize the opportunity for better prognostication and [getting] the patient on a targeted therapy or clinical trial," NeoGenomics Chief Medical Officer Derek Lyle said in an interview at the conference.
During the firm's sponsored workshop, Lyle defined comprehensive genomic profiling, or CGP, as involving a "relatively large number of genes" but, more importantly, targeting both DNA and RNA in order to capture the full scope of genomic alterations.
Having offered NGS testing for hematologic cancers for more than a decade, NeoGenomics has been privy to the evolution of the field. "We look at adoption by community oncologists, payor behavior, and guidelines inclusion … and all of these things are interrelated," Lyle said.
He noted that the company is now generally getting reimbursed for CGP through CMS but that it took the National Comprehensive Cancer Network about 10 years to mention sequencing for multiple genes in its guidelines.
Lyle argued that the siloing of guidelines for individual hematologic cancers is a clinical frustration. "My argument is, forget about that. If you have something that looks and smells like a myeloid-related neoplasm, don't look at it as an individual bucket category. Just order a comprehensive genomic profile."
"Under the microscope, these diseases have overlapping and, very often, nonspecific morphologic as well as genomic features," he added. If the initial clinical diagnosis isn't correct, a guidelines-mandated focused panel risks missing a potentially actionable alteration or relevant molecular diagnosis.
Unlike solid tumors, hematologic cancers have not been the target of much companion diagnostic development. Although there are some alterations that inform selection of a specific therapy, most of the content of a comprehensive sequencing panel for heme cancers relates to narrowing the diagnosis and making a prognosis to inform therapy.
Lyle said there is some irony there, considering that hematologic cancers were the face of some of the earliest biomarker-driven precision drugs. "At least on the myeloid side," where more targeted therapies have been developed, "there is a very, very strong argument to be made for the clinical utility of these genetic alterations," he said.
Lyle cited the case of an older patient with a working diagnosis of MDS, who then had a second sample tested using NeoGenomics' myeloid CGP assay, which detected a gene fusion that is never seen in MDS.
Ultimately, this led to a new diagnosis — a completely different disease category, for which there is a targeted therapy with promising efficacy available.
"When we launched our DNA/RNA test about a year and a half ago, we actually predicted that we would see more and more of these cases being worked up for myeloid disease-A or myeloid disease-B, but it actually turns out to be myeloid disease-C," Lyle added.
The company is currently working on a study, mining data from its first 18 months of testing and comparing the clinical indication for testing to the actual results. The goal is to determine how often the use of its assay leads to a change in diagnosis or management.
Dishant Kalra, head of precision medicine at Astellas Pharmaceuticals, said in a workshop sponsored by Foundation Medicine that the use of broad sequencing assays in drug development has been a challenge, considering that specific biomarkers are often included very early on in the study design.
"The initial decision is oftentimes a single biomarker, because when you're thinking globally, you want something that's straightforward, simple, low risk, widely available, and reimbursed or otherwise affordable."
That said, companies have started to realize that they also must think about the evolving market, he added.
Shirin Kalyan, an immunologist at the University of British Columbia, added that she believes CGP and narrower testing, including single-gene tests, "definitely should and will continue to deeply coexist."
While testing for single biomarkers is fast, is inexpensive, and can be done in-house, "you're only going to find what you're looking for," she said.
In her experience, CGP is gaining more popularity, she added, especially as turnaround time and cost come down.
"We don't get pushback at these types of conferences because you're sort of preaching to the choir," added Lyle. "When I'm talking about CGP, I see heads nodding out in the audience."
Many commercial payors, however, push back. "They're still stuck in this old-school way of thinking of less than 50 genes [versus] greater than 50 genes, and greater than 50 genes, for them, is a bridge too far," Lyle said.
Questioning the need for hundreds of mutations when only a handful might be immediately actionable is reasonable, he added. But in the context of hematologic cancers, where molecular testing is part of the diagnostic workup, there's strong impetus for "casting that wide net."
That's not to say that there isn't a need for narrower tests in the hematologic cancer space, though, Lyle acknowledged. NeoGenomics recently launched a smaller, rapid sequencing panel for AML, for example, that offers critical information with a turnaround time that better serves patients.
Robert Baker from the UK National Health Service's Health Services Laboratories, in a Thermo Fisher-sponsored workshop, described his lab's decision to move from PCR-based AML testing to a rapid sequencing approach using Thermo's Oncomine Myeloid Panel GX v2.
But having such a tool doesn't negate the need for CGP, Baker argued. "The people who want the rapid panels very much still want the comprehensive test."
However, no payor will pay for both tests, he added, which leaves heme-oncologists struggling with how to best manage their patients. "There's really just nothing we can do until the payors start to get on board," he said.