FDA Authorizes First Next-Generation Sequencing–Based Test to Detect Minimal Residual Disease in B-Cell ALL or Multiple Myeloma
The U.S. Food and Drug Administration (FDA) recently permitted marketing of the ClonoSEQ assay, a next-generation sequencing–based test for minimal residual disease in patients with B-cell acute lymphoblastic leukemia (ALL) or multiple myeloma.
“At the FDA, we’re continuing to maximize opportunities for innovation that can improve patient outcomes,” said FDA Commissioner Scott Gottlieb, MD. “[The] approval is an important step forward for patients [with] ALL and multiple myeloma. Determining whether a patient has residual cancer cells remaining after treatment provides information on how well a patient has responded to therapy and how long remission may last. Having a highly sensitive test available to measure minimal residual disease in ALL or multiple myeloma … can help providers manage their patients’ care.”
More About ClonSEQ
The ClonoSEQ assay is an in vitro diagnostic that uses multiplex polymerase chain reaction and next-generation sequencing to identify and quantify certain gene sequences in DNA extracted from bone marrow from patients with ALL or multiple myeloma. The ClonoSEQ assay measures the amount of minimal residual disease, and is capable of detecting minimal residual disease at levels below 1 in 1 million cells. This is a single-site assay collected by the patient’s provider and sent to Adaptive Biotechnologies Corporation for evaluation.
The FDA evaluated data to demonstrate clinical validity from a retrospective analysis of samples obtained from 3 previously conducted clinical studies including 273 patients with ALL, an ongoing study of 323 patients with multiple myeloma, and a study of 706 patients with multiple myeloma. For patients with ALL, the ClonoSEQ assay was used to assess minimal residual disease at various disease burden thresholds to show that the minimal residual disease level correlated with event-free survival.
Patients whose ClonoSEQ assay result was minimal residual disease–negative had longer event-free survival, whereas patients with higher minimal residual disease 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.
The FDA reviewed the ClonoSEQ assay through the de novo premarket review pathway, a regulatory pathway for novel, low-to-moderate–risk devices of a new type. Along with this authorization, the FDA is establishing special control criteria, which clarify the agency’s expectations in assuring the accuracy, reliability, and effectiveness of tests intended to be used as an aid to measure minimal residual disease to assess the change in burden of disease during and after treatment. These special controls, when met along with general controls, provide a reasonable assurance of safety and effectiveness for these tests.
This action also creates a new regulatory classification. Subsequent devices of the same type with the same intended use may go through the FDA’s 510(k) process, whereby devices can obtain marketing authorization by demonstrating substantial equivalence to a predicate device.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
