Silver Spring, MD (Press Release) – Today the U.S. Food and Drug Admin­istra­tion permitted mar­ket­ing of ClonoSEQ assay, a next generation sequencing (NGS)-based test for minimal residual disease (MRD) in patients with acute lymphoblastic leukemia (ALL) or multiple myeloma. MRD is a measure of the amount of cancer cells remaining in a person’s bone marrow.

“At the FDA, we’re continuing to maximize oppor­tuni­ties for inno­va­tion that can im­prove patient out­comes,” said FDA Com­mis­sioner Scott Gottlieb, M.D. “Today’s approval is an im­por­tant step for­ward for patients suffering from 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 patients can help providers man­age their patients’ care. The FDA is applying novel regu­la­tory ap­proaches to make sure that these rapidly evolving NGS tests are accurate and reliable. At the same time, we’re seeing more and more laboratory-developed tests seek mar­ket­ing authori­za­tion from the FDA. We’re doing as much as we can to ad­vance these oppor­tuni­ties for patients under our current author­i­ties. But we believe that to more fully unlock these inno­va­tions, we need to modernize the regu­la­tory framework for all in vitro clin­i­cal tests. We put for­ward one such plan. We believe such an ap­proach can promote the devel­op­ment of safe, effective tech­nolo­gies that have the greatest poten­tial to help us diagnose, treat and cure disease.”

B-Cell ALL is a rapidly progressing cancer that forms in the bone marrow and results in an in­­creased number of ab­nor­mal white blood cells in the bloodstream and bone marrow. Multiple myeloma is a cancer that begins in plasma cells, a type of white blood cell. Malignant plasma cells accumulate in the bone marrow, crowding out the normal plasma cells that help fight in­fec­tion. It is esti­mated that in 2018 approx­i­mately 6,000 people in the United States will be diag­nosed with ALL and approx­i­mately 31,000 new cases of multiple myeloma will be diag­nosed.

MRD is a general measure of the amount of cancer in the body (tumor burden), specifically the number of cancer cells that remain in a person’s bone marrow, either during or after treat­ment. Measuring MRD provides a tool to detect very low levels of tumor burden. MRD is useful to eval­u­ate in patients who have responded to ther­apy when their tumor burden is below what can be detected with standard methods. The detection of MRD is asso­ci­ated with recurrence of the disease in those patients. Cur­rently, providers test for MRD using diagnostics called flow cytometry assays or poly­mer­ase chain reac­tion (PCR)-based assays. Those methods are usually capable of measuring MRD down to 1 in 10,000 or 1 in 100,000 cells.

The ClonoSEQ assay is an in vitro diagnostic that uses multiplex PCR and NGS 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 MRD and is capable of detecting MRD 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 three 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 MRD at various disease burden thresh­olds to show that the MRD level correlated with event-free survival – the length of time, after treat­ment, that the patient remains free of certain com­pli­ca­tions or events. Patients whose ClonoSEQ assay result was MRD negative have 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 – the length of time during and after the treat­ment of a disease that a patient lives with the disease but it does not get worse – and disease-free survival—the length of time after pri­mary treat­ment for a cancer ends that the patient survives without any signs or symp­toms of that cancer.

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 criteria, called special controls, which clarify the agency’s ex­pec­ta­tions in assuring the accuracy, reliability and effectiveness of tests intended to be used as an aid to measure MRD 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, which means that 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 FDA granted market­ing authori­za­tion of ClonoSEQ assay to Adaptive Biotechnologies.

The FDA, an agency within the U.S. Department of Health and Human Services, pro­motes and pro­tects the public health by, among other things, assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological prod­ucts for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cos­metics, dietary supple­ments, prod­ucts that give off electronic radiation, and for regulating tobacco prod­ucts.