- FDA cleared the first test to use next generation sequencing (NGS) to detect cancer cells remaining in a patient’s bone marrow after treatment for two forms of blood cancer.
- Adaptive Biotechnologies' ClonoSEQ assay detects and monitors minimal residual disease (MRD) in patients with multiple myeloma and B-cell acute lymphoblastic leukemia. Residual cells that survive the initial cancer treatment are the main cause of relapse.
- FDA cleared the assay through its De Novo premarket review pathway for new low- to moderate-risk devices. The agency said it was establishing criteria called special controls with the authorization to clarify its expectations for accuracy, reliability and effectiveness of tests used to measure MRD for changes in disease burden during and after treatment.
Reductions in DNA sequencing costs are encouraging companies to develop NGS diagnostics that create a molecular profile of a patient's tumor to help inform treatment decisions. FDA in November approved the first NGS diagnostic, the FoundationOne CDx test, to detect genetic mutations in solid tumors. The test can detect mutations in 324 genes and two genomic signatures in any solid tumor. In March, CMS finalized Medicare coverage of diagnostic laboratory tests using NGS for patients with advanced cancer.
FDA Commissioner Scott Gottlieb, in a press release announcing the ClonoSEQ clearance, said the agency is seeing more laboratory-developed tests seek marketing authorization from FDA and is applying novel regulatory approaches to make sure that rapidly evolving tests are accurate and reliable. He noted FDA has proposed a plan to modernize the regulatory framework for all in vitro clinical tests, "to more fully unlock these innovations."
Testing for minimal residual disease to evaluate a patient’s response to therapy is also on the rise for guiding cancer treatment decisions. The ClonoSEQ identifies and quantifies specific DNA sequences found in malignant cells.
FDA said current tests for minimal residual disease use methods based on flow cytometry or polymerase chain reaction that are capable of measuring MRD down to 1 in 10,000 or 1 in 100,000 cells. The ClonoSEQ assay is capable of detecting MRD at levels below 1 in 1 million cells, the agency said.
"The sensitivity of the test is extremely important, as the number of cells remaining after treatment has been linked to patient outcomes," Paul Giusti, chief executive officer of the Multiple Myeloma Research Foundation, said in a press release from Adaptive Biotechnologies. "This clearance provides patients and physicians with access to a highly sensitive, standardized MRD test that can be an important tool in guiding treatment decisions."
There are more than 200,000 multiple myeloma and acute lymphoblastic leukemia patients in the United States, and more than 35,000 new cases are diagnosed each year, Adaptive Biotechnologies said.
FDA said it evaluated data to demonstrate clinical validity of the ClonoSEQ assay from a retrospective analysis of samples obtained from one study including 273 patients with acute lymphoblastic leukemia and two studies with groups of 323 and 706 patients with multiple myeloma.
Acute lymphoblastic leukemia patients whose ClonoSEQ assay result was MRD negative had longer event-free survival, while patients with higher MRD assay results had lower event-free survival rates. For patients with multiple myeloma, the ClonoSEQ assay demonstrated similar associations with progression-free survival and disease-free survival.
FDA noted its authorization of the assay creates a new regulatory classification, meaning subsequent devices of the same type with the same intended use may go through the agency’s 510(k) process to obtain marketing authorization by demonstrating substantial equivalence to a predicate device.