He continued, “I believe we are in the discovery phase of how best to use this end point [in] clinical decision making.Yes, we are incorporating MRD testing into routine practices more and more than in the past, mostly as a prognostic marker for long-term benefits — but the reality of the assay helping with decision making has yet to be explored.”
Other polymerase chain reaction (PCR)-based and flow cytometry-based assays have been evaluated, but their sensitivities never matched that of the NGS-based assays, Dr Nooka noted. They also require afresh bone marrow sample, making them less feasible in routine clinical settings.
“For now, clonoSEQ remains the tool of choice for MRD detection,” Dr Nooka said.
Dr Ravandi predicted that although uptake of clonoSEQ at cancer centers will not be immediate, it is a test “that will potentially supersede flow cytometry.” The tool has higher sensitivity than flow cytometry and cytometry requires “a significant degree of expertise that is not universally available,” he said. “With clonoSEQ, you don’t need as much interpretive expertise.”
And at MD Anderson, Dr Ravandi said, the staff uses flow cytometry for the most part. “In ALL, we do use NGS to look for mutations with a panel; there are data to suggest at least some mutations’ persistence is associated with AML relapse. There [are] no such data for ALL.”
NGS MRD assay results should not be interpreted in isolation, emphasized Christopher Hourigan, MD, PhD, chief, myeloid malignancies section, hematology branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
“Results must be carefully integrated with other clinical information, such as prior treatment and goals of care, by the treating physician in partnership with the individual patient,” Dr Hourigan said. “Secondly, it is important to differentiate between approved,well-validated, clinical tests and the great deal of research currently being done in laboratories throughout the world on clinical samples.”
Researchers are exploring other MRD assays, including the potential for peripheral blood sample testing(“liquid biopsy”), although no clinical data have yet been reported for such non solid-tumor MRD tests.
“Liquid biopsies generated a lot of interest due to the minimal invasiveness and the relative ease of a blood-based assay compared [with] a bone-marrow biopsy,” Dr Nooka said. “While evaluating circulating tumor cells and cell-free DNA for describing the mutational landscape and for disease monitoring is feasible,patients exhibit significant variability in the yields of tumor-derived CTCs and cfDNA, which makes it challenging from a MRD testing perspective.”