NEW YORK – Memorial Sloan Kettering Cancer Center (MSK) is in the process of implementing a new rapid sequencing-based cancer panel to complement ongoing comprehensive genomic profiling (CGP).
The assay, branded as MSK-React, is based on a new panel from Pillar Biosciences, recently launched as the OncoReveal Nexus. MSK-React masks two of the 21 genes in the panel and is available in separate reported formats for solid and hematological tumors.
"It's a bit of a Frankenpanel," said Mark Ewalt, MSKCC's associate medical director for laboratory operations in diagnostic molecular pathology. "Rather than make an indication-specific panel, we took all of our requests for rapid analytes, and we consolidated them onto one targeted panel and then designed it around the most frequently mutated regions there so that we could deploy this as a rapid assay for clinical use and trial enrollment."
The clinic will also run MSK-IMPACT (Integrated Mutation Profiling of Actionable Cancer Targets), its large CGP assay, in parallel. "So anything that's negative upfront on React we'll get more information on, so we can target those patients for earlier-phase clinical trials or feed that information into the research cohorts at MSK."
MSK has had its assay approved for clinical use by the New York State Department of Health and has begun a soft rollout of the panel in place of single-analyte PCR tests.
Duke University Health and the University of Southern California's Keck School of Medicine are also in the process of adopting the panel and collaborated with Pillar on the assay design, Pillar Chief Marketing Officer Brian Wright said in an email.
"While our intended use of this assay is multifaceted, our primary aim is to streamline single gene testing — currently performed using several different methodologies — to a single, rapid NGS platform," Sarah Rapisardo, director of test development at Duke University Health System Clinical Labs, said in an email. "We are seeking rapid results for clinically actionable genes that drive therapy selection, with an initial focus on hematological malignancies. We are increasing workflow efficiencies on a platform with greater scalability, a more rapid turnaround time, and, in many cases, greater sensitivity."
Ewalt further noted that balancing the desire for rapid turnaround time with the desire for comprehensive testing "is a challenge for the field globally." But what this will cost and who will pay for parallel testing remains to be seen.
MSK is a pioneer in the field of sequencing-based tumor profiling, nabbing the first US Food and Drug Administration authorization for such a test in 2017 with MSK-IMPACT. Now available for both solid and hematological tumors, the CGP assays evaluate 505 and 400 genes, respectively, looking for protein-coding mutations, copy number alterations, and other variation in cancer-associated genes that can inform therapy selection.
"Eight to 10 years ago, oncologists wanted the biggest test possible," Ewalt said. "Now, there's a little more nuanced approach to this." CGP is still important, especially for getting a total workup for patients and to contribute to the hospital's research mission. But targeted therapies are now available as frontline treatments and clinicians want genomic information as soon as possible. With a turnaround time of as little as three days — compared to about two weeks for CGP — the hope is that this type of assays can help clinicians reduce the time to settling on the optimal treatment for a patient, whether that's targeted therapy or more traditional chemotherapy.
OncoReveal Nexus is a PCR-based targeted panel that analyzes 111 total targets across 21 genes. That includes mutation hotspots in 20 genes and full coverage of TP53 and FLT3 internal tandem duplications. The assay can work with samples from blood or from formalin-fixed, paraffin-embedded samples. Pillar recommends sequencing with at least 615,000 reads. List price for a 24-reaction kit is $5,000, or $208 per sample.
MSK will primarily run the assay on the Illumina MiSeq instrument, a smaller benchtop platform, with the Micro reagent kit. "This allows us to batch 13 clinical samples and controls," Ewalt said. With a 19-hour run time, an "ideal" three-day workflow sees sequencing data ready by noon on day two and a report by the end of day three. Over weekends, when the lab isn't open, they'll plan to batch more samples on a bigger v2 flow cell, which takes about 27 hours, he said.
MSK does not yet have any studies set up to evaluate the effects of getting results with a smaller, faster assay. "For right now, we're still sort of just rolling it out to try to meet the clinical desires."
Duke is not planning to use the assay in parallel with CGP, Rapisardo said. "We will report a subset of genes in the panel, plus added custom content for clinically relevant pharmacogenomic targets." They're validating it now with plans to roll it out early next year.
MSK completed its validation in April and received conditional approval from New York in June. A soft rollout began in late August, replacing single-analyte testing in lung cancer. "We found this [assay] very robust," Ewalt said. Pillar recommends an input of 10 ng of DNA; however, input dilution studies suggested "adequate performance" at 2.5 ng and above, he said. "If it's really desperate and with an attending review, we may go lower," he said. That's compared to a goal of 250 ng input for MSK-IMPACT and a lower limit of 50 ng. "We validated on cell-free DNA as well as genomic DNA from a variety of sources, and it works quite well," he added.
The small panel size makes it fast but precludes the test from analyzing some "emerging biomarkers" such as tumor mutational burden, Ewalt noted. "There are going to be intrinsic limitations," he said.
How healthcare systems will bill for the test remains unclear. "We have worked with our billing and revenue office to review coverage based on insurance payors and plans," Rapisardo said. Ewalt noted that many payors will not cover two sequencing-based tests for the same sample, but did not know whether MSK would eat the costs or pass them on to the patient.
"Clinical guidelines are starting to push for faster and faster turnaround times, and the National Comprehensive Cancer Network and others are starting to recommend results very quickly, but also increasing numbers of biomarkers to get those results," he said. "I really hope that payors can find a way to reimburse labs for a rapid assessment that meets the guidelines, as well as continuing to support the reimbursement for comprehensive genome profiling. I think there's value in both."